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this.src = '//a.academia-assets.com/images/s200_no_pic.png';" width="200" height="200" src="https://0.academia-photos.com/69159441/17943915/165874500/s200_dr_naglaa.ibrahim.jpg" /></a></div><div class="suggested-user-card__user-info"><a class="suggested-user-card__user-info__header ds2-5-body-sm-bold ds2-5-body-link" href="https://aswu.academia.edu/NaglaaIbrahim">Dr Naglaa Ibrahim</a><p class="suggested-user-card__user-info__subheader ds2-5-body-xs">Aswan University</p></div></div></ul></div><div class="ri-section"><div class="ri-section-header"><span>Interests</span></div><div class="ri-tags-container"><a data-click-track="profile-user-info-expand-research-interests" data-has-card-for-ri-list="37187764" href="https://www.academia.edu/Documents/in/Higher_Education_Policy"><div id="js-react-on-rails-context" style="display:none" 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Education"]}" data-trace="false" data-dom-id="Pill-react-component-b4208b71-28a9-4d13-a948-cc2c9c7038a7"></div> <div id="Pill-react-component-b4208b71-28a9-4d13-a948-cc2c9c7038a7"></div> </a><a data-click-track="profile-user-info-expand-research-interests" data-has-card-for-ri-list="37187764" href="https://www.academia.edu/Documents/in/Learning_And_Teaching_In_Higher_Education"><div class="js-react-on-rails-component" style="display:none" data-component-name="Pill" data-props="{"color":"gray","children":["Learning And Teaching In Higher Education"]}" data-trace="false" data-dom-id="Pill-react-component-c004145f-5115-430b-bf3a-f65f4a272c3e"></div> <div id="Pill-react-component-c004145f-5115-430b-bf3a-f65f4a272c3e"></div> </a><a data-click-track="profile-user-info-expand-research-interests" data-has-card-for-ri-list="37187764" href="https://www.academia.edu/Documents/in/Assessment"><div class="js-react-on-rails-component" style="display:none" data-component-name="Pill" data-props="{"color":"gray","children":["Assessment"]}" data-trace="false" data-dom-id="Pill-react-component-54be2fad-154f-49ed-b813-4d958774ad09"></div> <div id="Pill-react-component-54be2fad-154f-49ed-b813-4d958774ad09"></div> </a><a data-click-track="profile-user-info-expand-research-interests" data-has-card-for-ri-list="37187764" href="https://www.academia.edu/Documents/in/Higher_Education"><div class="js-react-on-rails-component" style="display:none" data-component-name="Pill" data-props="{"color":"gray","children":["Higher Education"]}" data-trace="false" data-dom-id="Pill-react-component-98079ba5-bae8-499b-82d4-e5e3a8bf2750"></div> <div id="Pill-react-component-98079ba5-bae8-499b-82d4-e5e3a8bf2750"></div> </a></div></div></div></div><div class="right-panel-container"><div class="user-content-wrapper"><div class="uploads-container" id="social-redesign-work-container"><div class="upload-header"><h2 class="ds2-5-heading-sans-serif-xs">Uploads</h2></div><div class="documents-container backbone-social-profile-documents" style="width: 100%;"><div class="u-taCenter"></div><div class="profile--tab_content_container js-tab-pane tab-pane active" id="all"><div class="profile--tab_heading_container js-section-heading" data-section="Papers" id="Papers"><h3 class="profile--tab_heading_container">Papers by Philip Burcham</h3></div><div class="js-work-strip profile--work_container" data-work-id="124940232"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/124940232/Faculty_of_1000_evaluation_for_Pharmacometabonomic_identification_of_a_significant_host_microbiome_metabolic_interaction_affecting_human_drug_metabolism"><img alt="Research paper thumbnail of Faculty of 1000 evaluation for Pharmacometabonomic identification of a significant host-microbiome metabolic interaction affecting human drug metabolism" class="work-thumbnail" src="https://attachments.academia-assets.com/119072427/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/124940232/Faculty_of_1000_evaluation_for_Pharmacometabonomic_identification_of_a_significant_host_microbiome_metabolic_interaction_affecting_human_drug_metabolism">Faculty of 1000 evaluation for Pharmacometabonomic identification of a significant host-microbiome metabolic interaction affecting human drug metabolism</a></div><div class="wp-workCard_item"><span>F1000 - Post-publication peer review of the biomedical literature</span><span>, 2009</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="a3dba70f79a0355c3d8ebff1d81079f7" class="wp-workCard--action" rel="nofollow" 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window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=124940232]").text(description); $(".js-view-count[data-work-id=124940232]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 124940232; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='124940232']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "a3dba70f79a0355c3d8ebff1d81079f7" } } $('.js-work-strip[data-work-id=124940232]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":124940232,"title":"Faculty of 1000 evaluation for Pharmacometabonomic identification of a significant host-microbiome metabolic interaction affecting human drug 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Burcham","url":"https://independent.academia.edu/PhilipBurcham"},"attachments":[{"id":119072427,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/119072427/thumbnails/1.jpg","file_name":"1165212.pdf","download_url":"https://www.academia.edu/attachments/119072427/download_file","bulk_download_file_name":"Faculty_of_1000_evaluation_for_Pharmacom.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/119072427/1165212-libre.pdf?1729590252=\u0026response-content-disposition=attachment%3B+filename%3DFaculty_of_1000_evaluation_for_Pharmacom.pdf\u0026Expires=1740224218\u0026Signature=cc5FZQReTUwZow4w79kO8OBFMuONjGTtTh38NGUZFlIxwQMsy6IB1VUmnaAwrc3Cn~iVVokxMtbAzmbi4lllynJmB76tTQGPHS~4ezUsyTFyln5APRLjfBZU8tgvTt7f7ENf1iEPud8XmZhuxSSRk3IBYTt66XuhN60~cWuEWjurBhAo-if0x0~b~AHCId6cH7KNnmbBoh5eL-ksz2ehtd6pvlg~Qjz6Q2C4fiGIOoqeel2MjAl6D2L0wpmx24o3vgmY5cLa8Tzf3pvJdipPlUQru3kG7naIMozP-8cFt1KDWfjKZAP9VlOSCH7R5taDXJMR0pp6jGvFDrhaZl-HRA__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="120657145"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/120657145/Hydralazine_Inhibits_Rapid_Acrolein_Induced_Protein_Oligomerization_Role_of_Aldehyde_Scavenging_and_Adduct_Trapping_in_Cross_Link_Blocking_and_Cytoprotection"><img alt="Research paper thumbnail of Hydralazine Inhibits Rapid Acrolein-Induced Protein Oligomerization: Role of Aldehyde Scavenging and Adduct Trapping in Cross-Link Blocking and Cytoprotection" class="work-thumbnail" src="https://attachments.academia-assets.com/115737399/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/120657145/Hydralazine_Inhibits_Rapid_Acrolein_Induced_Protein_Oligomerization_Role_of_Aldehyde_Scavenging_and_Adduct_Trapping_in_Cross_Link_Blocking_and_Cytoprotection">Hydralazine Inhibits Rapid Acrolein-Induced Protein Oligomerization: Role of Aldehyde Scavenging and Adduct Trapping in Cross-Link Blocking and Cytoprotection</a></div><div class="wp-workCard_item"><span>Molecular Pharmacology</span><span>, 2005</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Hydralazine strongly suppresses the toxicity of acrolein, a reactive aldehyde that contributes to...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Hydralazine strongly suppresses the toxicity of acrolein, a reactive aldehyde that contributes to numerous health disorders. At least two mechanisms may underlie the cytoprotection, both of which involve the nucleophilic hydrazine possessed by hydralazine. Under the simplest scenario, hydralazine directly scavenges free acrolein, decreasing intracellular acrolein availability and thereby suppressing macromolecular adduction. In a second "adduct-trapping" mechanism, the drug forms hydrazones with acrolein-derived Michael adducts in cell proteins, preventing secondary reactions of adducted proteins that may trigger cell death. To identify the most important mechanism, we explored these two pathways in mouse hepatocytes poisoned with the acrolein precursor allyl alcohol. Intense concentration-dependent adduct-trapping in cell proteins accompanied the suppression of toxicity by hydralazine. However, protective concentrations of hydralazine did not alter extracellular free acrolein levels, cellular glutathione loss or protein carbonylation, suggesting the cytoprotection is not due to minimization of intracellular acrolein availability. To explore ways whereby adduct-trapping might confer cytoprotection, the effect of hydralazine on acrolein-induced protein cross-linking was examined. Using bovine pancreas ribonuclease A as a model protein, acrolein caused rapid time-and concentration-dependent cross-linking, with dimerized protein detectable within 45 min of commencing protein modification. Lysine adduction in monomeric protein preceded the appearance of oligomers, while reductive methylation of protein amine groups abolished both adduction and oligomerization. Hydralazine inhibited cross-linking if added 30 min after commencing acrolein exposure but was ineffective if added after a 90 min delay. Adduct-trapping closely accompanied the inhibition of This article has not been copyedited and formatted. The final version may differ from this version.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="d936e0574caa2a6bfd14611c49127f79" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":115737399,"asset_id":120657145,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/115737399/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="120657145"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="120657145"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 120657145; 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="115243773"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/115243773/Faculty_of_1000_evaluation_for_Assessment_of_Protein_Binding_of_5_Hydroxythalidomide_Bioactivated_in_Humanized_Mice_with_Human_P450_3A_Chromosome_or_Hepatocytes_by_Two_Dimensional_Electrophoresis_Accelerator_Mass_Spectrometry"><img alt="Research paper thumbnail of Faculty of 1000 evaluation for Assessment of Protein Binding of 5-Hydroxythalidomide Bioactivated in Humanized Mice with Human P450 3A-Chromosome or Hepatocytes by Two-Dimensional Electrophoresis/Accelerator Mass Spectrometry" class="work-thumbnail" src="https://attachments.academia-assets.com/111707902/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/115243773/Faculty_of_1000_evaluation_for_Assessment_of_Protein_Binding_of_5_Hydroxythalidomide_Bioactivated_in_Humanized_Mice_with_Human_P450_3A_Chromosome_or_Hepatocytes_by_Two_Dimensional_Electrophoresis_Accelerator_Mass_Spectrometry">Faculty of 1000 evaluation for Assessment of Protein Binding of 5-Hydroxythalidomide Bioactivated in Humanized Mice with Human P450 3A-Chromosome or Hepatocytes by Two-Dimensional Electrophoresis/Accelerator Mass Spectrometry</a></div><div class="wp-workCard_item"><span>F1000 - Post-publication peer review of the biomedical literature</span><span>, 2017</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Bioactivation of 5-hydroxy-[carbonyl-14 C]thalidomide, a known metabolite of thalidomide, by huma...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Bioactivation of 5-hydroxy-[carbonyl-14 C]thalidomide, a known metabolite of thalidomide, by human artificial or native cytochrome P450 3A enzymes, and nonspecific binding in livers of mice was assessed using two-dimensional electrophoresis combined with accelerator mass spectrometry. The apparent major target proteins were liver microsomal cytochrome c oxidase subunit 6B1 and ATP synthase subunit α in mice containing humanized P450 3A genes or transplanted humanized liver. Liver cytosolic retinal dehydrogenase 1 and glutathione transferase *</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="10770a95e07353d0805ad664ff09413b" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":111707902,"asset_id":115243773,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/111707902/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="115243773"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="115243773"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 115243773; 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="106827461"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/106827461/Faculty_of_1000_evaluation_for_Aristolochic_acid_associated_urothelial_cancer_in_Taiwan"><img alt="Research paper thumbnail of Faculty of 1000 evaluation for Aristolochic acid-associated urothelial cancer in Taiwan" class="work-thumbnail" src="https://attachments.academia-assets.com/105806826/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/106827461/Faculty_of_1000_evaluation_for_Aristolochic_acid_associated_urothelial_cancer_in_Taiwan">Faculty of 1000 evaluation for Aristolochic acid-associated urothelial cancer in Taiwan</a></div><div class="wp-workCard_item"><span>F1000 - Post-publication peer review of the biomedical literature</span><span>, 2012</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="8eec22ce0b93fa04db1671f19b325dbe" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":105806826,"asset_id":106827461,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/105806826/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="106827461"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="106827461"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 106827461; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=106827461]").text(description); $(".js-view-count[data-work-id=106827461]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 106827461; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='106827461']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="50087456"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/50087456/Differences_in_Lysine_Adduction_by_Acrolein_and_Methyl_Vinyl_Ketone_Implications_for_Cytotoxicity_in_Cultured_Hepatocytes"><img alt="Research paper thumbnail of Differences in Lysine Adduction by Acrolein and Methyl Vinyl Ketone: Implications for Cytotoxicity in Cultured Hepatocytes" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/50087456/Differences_in_Lysine_Adduction_by_Acrolein_and_Methyl_Vinyl_Ketone_Implications_for_Cytotoxicity_in_Cultured_Hepatocytes">Differences in Lysine Adduction by Acrolein and Methyl Vinyl Ketone: Implications for Cytotoxicity in Cultured Hepatocytes</a></div><div class="wp-workCard_item"><span>Chemical Research in Toxicology</span><span>, 2005</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Acrolein is a highly toxic environmental pollutant that readily alkylates the epsilon-amino group...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Acrolein is a highly toxic environmental pollutant that readily alkylates the epsilon-amino group of lysine residues in proteins. In model systems, such chemistry involves sequential addition of two acrolein molecules to a given nitrogen, forming bis-Michael-adducted species that undergo aldol condensation and dehydration to form Nepsilon-(3-formyl-3,4-dehydropiperidino)lysine. Whether this ability to form cyclic adducts participates in the toxicity of acrolein is unknown. To address this issue, we compared the chemistry of protein adduction by acrolein to that of its close structural analogue methyl vinyl ketone, expecting that the alpha-methyl group would hinder the intramolecular cyclization of any bis-adducted species formed by methyl vinyl ketone. Both acrolein and methyl vinyl ketone displayed comparable protein carbonylating activity during in vitro studies with the model protein bovine serum albumin, confirming the alpha,beta,-unsaturated bond of both compounds is an efficient Michael acceptor for protein nucleophiles. However, differences in adduction chemistry became apparent during the use of electrospray ionization-MS to monitor reaction products in a lysine-containing peptide after modification by each compound. For example, although a Schiff base adduct was detected following reaction of the peptide with acrolein, an analogous species was not formed by methyl vinyl ketone. Furthermore, while ions corresponding to mono- and bis-Michael adducts were detected at the N-terminus and lysine residues following peptide modification by both carbonyls, only acrolein modification generated ions attributable to cyclic adducts. Despite these differences in adduction chemistry, in mouse hepatocytes, the two compounds exhibited very comparable abilities to induce rapid, concentration-dependent cell death as well as protein carbonylation. These findings suggest that the acute toxicity of short-chain alpha,beta-unsaturated carbonyl compounds involves their ability to form acyclic Michael addition adducts rather than Schiff conjugates or heterocyclic adducts.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="50087456"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="50087456"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 50087456; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=50087456]").text(description); $(".js-view-count[data-work-id=50087456]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 50087456; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='50087456']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); 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</script> <div class="js-work-strip profile--work_container" data-work-id="49772192"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/49772192/Reactivity_with_Tris_hydroxymethyl_aminomethane_Confounds_Immunodetection_of_Acrolein_Adducted_Proteins"><img alt="Research paper thumbnail of Reactivity with Tris(hydroxymethyl)aminomethane Confounds Immunodetection of Acrolein-Adducted Proteins" class="work-thumbnail" src="https://attachments.academia-assets.com/68011290/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/49772192/Reactivity_with_Tris_hydroxymethyl_aminomethane_Confounds_Immunodetection_of_Acrolein_Adducted_Proteins">Reactivity with Tris(hydroxymethyl)aminomethane Confounds Immunodetection of Acrolein-Adducted Proteins</a></div><div class="wp-workCard_item"><span>Chemical Research in Toxicology</span><span>, 2003</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The toxic R,-unsaturated aldehyde acrolein readily attacks proteins, generating adducts at cystei...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The toxic R,-unsaturated aldehyde acrolein readily attacks proteins, generating adducts at cysteine, histidine, and lysine residues. In this study, rabbit antiserum was raised against acrolein-modified keyhole limpet hemocyanin in the expectation that it would allow immunodetection of adducted proteins in biological samples. Using slot-blot and enzyme-linked immunosorbent assays, the antiserum detected acrolein-modified protein with high sensitivity and specificity. Adduct immunodetection was strongly inhibited by acrolein-modified polylysine but not polyhistidine. Efforts to develop a Western blotting method for detecting adducted proteins in cell lysates were hampered by irreproducible outcomes, evidently due to adduct instability during SDS-PAGE. Indeed, adducts generated via brief exposure of a model protein to acrolein displayed pH-and concentration-dependent instability to tris(hydroxymethyl)aminomethane (Tris), a nucleophilic buffer used in protein electrophoresis. The effect was most striking when Tris solutions were buffered to pH 8.0 and higher. In contrast, adducts formed during extended exposure to acrolein (g60 min) were completely stable to Tris. The time dependence of susceptibility raised the possibility that Tris interfered with specific steps in lysine modification, which involves stepwise Michael addition of two molecules of acrolein to the same residue, followed by condensation and dehydration to form a heterocyclic adduct, N-(3-formyl-3,4-dehydropiperidino)lysine. We hypothesize that carbonyl-retaining Michael adducts may react with Tris by forming imines with the primary amine of the buffer. Consistent with this idea, triethanolamine, a tertiary amine buffer unable to form imines, had no effect on acrolein-adducted protein. These effects of Tris may explain difficulties in the detection of acrolein-adducted proteins during conventional Western blotting procedures.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="abfb8857ae86c5981b28c859efcfcfc1" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":68011290,"asset_id":49772192,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/68011290/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="49772192"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="49772192"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 49772192; 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="46619372"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/46619372/Protein_Adduct_Trapping_by_Hydrazinophthalazine_Drugs_Mechanisms_of_Cytoprotection_Against_Acrolein_Mediated_Toxicity"><img alt="Research paper thumbnail of Protein Adduct-Trapping by Hydrazinophthalazine Drugs: Mechanisms of Cytoprotection Against Acrolein-Mediated Toxicity" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/46619372/Protein_Adduct_Trapping_by_Hydrazinophthalazine_Drugs_Mechanisms_of_Cytoprotection_Against_Acrolein_Mediated_Toxicity">Protein Adduct-Trapping by Hydrazinophthalazine Drugs: Mechanisms of Cytoprotection Against Acrolein-Mediated Toxicity</a></div><div class="wp-workCard_item"><span>Molecular Pharmacology</span><span>, 2004</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="46619372"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="46619372"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 46619372; 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dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=46619372]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":46619372,"title":"Protein Adduct-Trapping by Hydrazinophthalazine Drugs: Mechanisms of Cytoprotection Against Acrolein-Mediated Toxicity","internal_url":"https://www.academia.edu/46619372/Protein_Adduct_Trapping_by_Hydrazinophthalazine_Drugs_Mechanisms_of_Cytoprotection_Against_Acrolein_Mediated_Toxicity","owner_id":37187764,"coauthors_can_edit":true,"owner":{"id":37187764,"first_name":"Philip","middle_initials":null,"last_name":"Burcham","page_name":"PhilipBurcham","domain_name":"independent","created_at":"2015-10-28T21:31:21.614-07:00","display_name":"Philip Burcham","url":"https://independent.academia.edu/PhilipBurcham"},"attachments":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="17446909"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/17446909/Influenza_A_infection_attenuates_relaxation_responses_of_mouse_tracheal_smooth_muscle_evoked_by_acrolein"><img alt="Research paper thumbnail of Influenza A infection attenuates relaxation responses of mouse tracheal smooth muscle evoked by acrolein" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/17446909/Influenza_A_infection_attenuates_relaxation_responses_of_mouse_tracheal_smooth_muscle_evoked_by_acrolein">Influenza A infection attenuates relaxation responses of mouse tracheal smooth muscle evoked by acrolein</a></div><div class="wp-workCard_item"><span>Biochemical pharmacology</span><span>, Jan 15, 2015</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The airway epithelium is an important source of relaxant mediators, and damage to the epithelium ...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The airway epithelium is an important source of relaxant mediators, and damage to the epithelium caused by respiratory tract viruses may contribute to airway hyperreactivity. The aim of this study was to determine whether influenza A-induced epithelial damage would modulate relaxation responses evoked by acrolein, a toxic and prevalent component of smoke. Male BALB/c mice were inoculated intranasally with influenza A/PR-8/34 (VIRUS-infected) or allantoic fluid (SHAM-infected). On day 4 post-inoculation, isometric tension recording studies were conducted on carbachol pre-contracted tracheal segments isolated from VIRUS and SHAM mice. Relaxant responses to acrolein (30μM) were markedly smaller in VIRUS segments compared to SHAM segments (2±1% relaxation vs. 28±5%, n=14, p&lt;0.01). Similarly, relaxation responses of VIRUS segments to the neuropeptide substance P (SP) were greatly attenuated (1±1% vs. 47±6% evoked by 1nM SP, n=14, p&lt;0.001). Consistent with epithelial damage, PGE2 re...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="17446909"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="17446909"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 17446909; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=17446909]").text(description); $(".js-view-count[data-work-id=17446909]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 17446909; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='17446909']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=17446909]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":17446909,"title":"Influenza A infection attenuates relaxation responses of mouse tracheal smooth muscle evoked by acrolein","internal_url":"https://www.academia.edu/17446909/Influenza_A_infection_attenuates_relaxation_responses_of_mouse_tracheal_smooth_muscle_evoked_by_acrolein","owner_id":37187764,"coauthors_can_edit":true,"owner":{"id":37187764,"first_name":"Philip","middle_initials":null,"last_name":"Burcham","page_name":"PhilipBurcham","domain_name":"independent","created_at":"2015-10-28T21:31:21.614-07:00","display_name":"Philip Burcham","url":"https://independent.academia.edu/PhilipBurcham"},"attachments":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="17446908"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/17446908/Optimisation_of_the_comet_genotoxicity_assay_in_freshly_isolated_murine_hepatocytes_detection_of_strong_in_vitro_DNA_damaging_properties_for_styrene"><img alt="Research paper thumbnail of Optimisation of the comet genotoxicity assay in freshly isolated murine hepatocytes: detection of strong in vitro DNA damaging properties for styrene" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/17446908/Optimisation_of_the_comet_genotoxicity_assay_in_freshly_isolated_murine_hepatocytes_detection_of_strong_in_vitro_DNA_damaging_properties_for_styrene">Optimisation of the comet genotoxicity assay in freshly isolated murine hepatocytes: detection of strong in vitro DNA damaging properties for styrene</a></div><div class="wp-workCard_item"><span>Toxicology in Vitro</span><span>, 2004</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">While the comet assay is used to detect DNA damage in isolated cells following exposure to chemic...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">While the comet assay is used to detect DNA damage in isolated cells following exposure to chemicals in vitro, few publications report the use of the procedure in liver cells isolated from mice. Our initial efforts to use the assay to assess DNA damage in mouse hepatocytes maintained on collagen-coated dishes were hampered by high levels of baseline damage in</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="17446908"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="17446908"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 17446908; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=17446908]").text(description); $(".js-view-count[data-work-id=17446908]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 17446908; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='17446908']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=17446908]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":17446908,"title":"Optimisation of the comet genotoxicity assay in freshly isolated murine hepatocytes: detection of strong in vitro DNA damaging properties for styrene","internal_url":"https://www.academia.edu/17446908/Optimisation_of_the_comet_genotoxicity_assay_in_freshly_isolated_murine_hepatocytes_detection_of_strong_in_vitro_DNA_damaging_properties_for_styrene","owner_id":37187764,"coauthors_can_edit":true,"owner":{"id":37187764,"first_name":"Philip","middle_initials":null,"last_name":"Burcham","page_name":"PhilipBurcham","domain_name":"independent","created_at":"2015-10-28T21:31:21.614-07:00","display_name":"Philip Burcham","url":"https://independent.academia.edu/PhilipBurcham"},"attachments":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="17446907"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/17446907/UDP_glucuronosyltransferase_dependent_bioactivation_of_clofibric_acid_to_a_DNA_damaging_intermediate_in_mouse_hepatocytes"><img alt="Research paper thumbnail of UDP-glucuronosyltransferase-dependent bioactivation of clofibric acid to a DNA-damaging intermediate in mouse hepatocytes" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/17446907/UDP_glucuronosyltransferase_dependent_bioactivation_of_clofibric_acid_to_a_DNA_damaging_intermediate_in_mouse_hepatocytes">UDP-glucuronosyltransferase-dependent bioactivation of clofibric acid to a DNA-damaging intermediate in mouse hepatocytes</a></div><div class="wp-workCard_item"><span>Chemico-biological Interactions</span><span>, 2003</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Glucuronidation of a number of carboxyl-containing drugs generates reactive acyl glucuronide meta...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Glucuronidation of a number of carboxyl-containing drugs generates reactive acyl glucuronide metabolites. These electrophilic species alkylate cell proteins and may be implicated in the pathogenesis of a number of toxic syndromes seen in patients receiving the parent aglycones. Whether acyl glucuronides also attack nuclear DNA is unknown, although the acyl glucuronide formed from clofibric acid was recently found to decrease</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="17446907"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="17446907"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 17446907; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=17446907]").text(description); $(".js-view-count[data-work-id=17446907]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 17446907; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='17446907']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); 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</script> <div class="js-work-strip profile--work_container" data-work-id="8552502"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/8552502/Aldehyde_sequestering_drugs_tools_for_studying_protein_damage_by_lipid_peroxidation_products"><img alt="Research paper thumbnail of Aldehyde-sequestering drugs: tools for studying protein damage by lipid peroxidation products" class="work-thumbnail" src="https://attachments.academia-assets.com/48057497/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/8552502/Aldehyde_sequestering_drugs_tools_for_studying_protein_damage_by_lipid_peroxidation_products">Aldehyde-sequestering drugs: tools for studying protein damage by lipid peroxidation products</a></div><div class="wp-workCard_item wp-workCard--coauthors"><span>by </span><span><a class="" data-click-track="profile-work-strip-authors" href="https://independent.academia.edu/SimonPyke">Simon Pyke</a>, <a class="" data-click-track="profile-work-strip-authors" href="https://uq.academia.edu/FrankFontaine">Frank Fontaine</a>, and <a class="" data-click-track="profile-work-strip-authors" href="https://independent.academia.edu/PhilipBurcham">Philip Burcham</a></span></div><div class="wp-workCard_item"><span>Toxicology</span><span>, 2002</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Elevated levels of reactive a,b-unsaturated aldehydes (e.g. malondialdehyde, 4-hydroxynonenal and...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Elevated levels of reactive a,b-unsaturated aldehydes (e.g. malondialdehyde, 4-hydroxynonenal and acrolein) in the affected tissues of various degenerative conditions suggest these substances are active propagators of the disease process. One experimental approach to attenuating damage by these intermediates employs 'aldehyde-sequestering drugs' as sacrificial nucleophiles, thereby sparing cell macromolecules and perhaps slowing disease progression. Drugs with demonstrated trapping activity toward lipid-derived aldehydes include various amine compounds such as aminoguanidine, carnosine and pyridoxamine. We have focused on identifying scavengers of acrolein, perhaps the most toxic aldehyde formed during lipid peroxidation cascades. Various phthalazine compounds (hydralazine and dihydralazine) were found to trap acrolein readily, forming hydrazone derivatives in a rapid Schiff-type reaction. These compounds strongly protect against acrolein-mediated toxicity in isolated hepatocytes.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="69898b0f43c0c2fcb7772c3589cfb8ac" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":48057497,"asset_id":8552502,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/48057497/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="8552502"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="8552502"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 8552502; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=8552502]").text(description); $(".js-view-count[data-work-id=8552502]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 8552502; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='8552502']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "69898b0f43c0c2fcb7772c3589cfb8ac" } } $('.js-work-strip[data-work-id=8552502]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":8552502,"title":"Aldehyde-sequestering drugs: tools for studying protein damage by lipid peroxidation products","internal_url":"https://www.academia.edu/8552502/Aldehyde_sequestering_drugs_tools_for_studying_protein_damage_by_lipid_peroxidation_products","owner_id":17601503,"coauthors_can_edit":true,"owner":{"id":17601503,"first_name":"Simon","middle_initials":null,"last_name":"Pyke","page_name":"SimonPyke","domain_name":"independent","created_at":"2014-09-29T08:58:16.374-07:00","display_name":"Simon Pyke","url":"https://independent.academia.edu/SimonPyke"},"attachments":[{"id":48057497,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/48057497/thumbnails/1.jpg","file_name":"s0300-483x_2802_2900287-120160814-13132-1k4wcvv.pdf","download_url":"https://www.academia.edu/attachments/48057497/download_file","bulk_download_file_name":"Aldehyde_sequestering_drugs_tools_for_st.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/48057497/s0300-483x_2802_2900287-120160814-13132-1k4wcvv-libre.pdf?1471239482=\u0026response-content-disposition=attachment%3B+filename%3DAldehyde_sequestering_drugs_tools_for_st.pdf\u0026Expires=1740220298\u0026Signature=AYwlMYughGOAbSqDdl6rw~-t-kzTtha0sm0Mzkv0-28aMPqlsCkpcDFYEIBPJLrMaaQu~d~UZcQkV4mwbVkIVWcp4JZrnXD5P~MiMZrZVA4rv6AeKJrcqm2sZC8zkU8sV7Of~d4Ywrcpdvt9n05dwuaA8bSjENY9l7cD7MBoBE7bV6PpYY7FPTvOmh52RFv2TWFDxWA7zQ9ZFS~uw6HbpgXgfOuVLQRWUg2Yj6H-vNLCsfRdnG-waKso8Biwk3a4h2OlJJtzhSXC5awVUe8PUWcu3PkfL8fJsROo6OqzOxyFY-g8UhF8NiDR3GVZXwjaBCfnD~y-edPMpycHwOqtDA__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="17446906"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/17446906/Clofibrate_Induced_in_Vitro_Hepatoprotection_against_Acetaminophen_Is_Not_Due_to_Altered_Glutathione_Homeostasis"><img alt="Research paper thumbnail of Clofibrate-Induced in Vitro Hepatoprotection against Acetaminophen Is Not Due to Altered Glutathione Homeostasis" class="work-thumbnail" src="https://attachments.academia-assets.com/39513368/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/17446906/Clofibrate_Induced_in_Vitro_Hepatoprotection_against_Acetaminophen_Is_Not_Due_to_Altered_Glutathione_Homeostasis">Clofibrate-Induced in Vitro Hepatoprotection against Acetaminophen Is Not Due to Altered Glutathione Homeostasis</a></div><div class="wp-workCard_item"><span>Toxicological Sciences</span><span>, 2000</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Prior induction of peroxisome proliferation protects mice against the in vivo hepatotoxicity of a...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Prior induction of peroxisome proliferation protects mice against the in vivo hepatotoxicity of acetaminophen and various other bioactivation-dependent toxicants. The mechanisms underlying such chemoresistance are poorly understood, although they have been suggested to involve alterations in glutathione homeostasis. To clarify the role of glutathione in this phenomenon, we isolated hepatocytes from mice in which hepatic peroxisome proliferation had been induced with clofibrate. The cells were incubated with a range of acetaminophen concentrations and the extent of cell killing after up to 8 h was assessed by measuring lactate dehydrogenase leakage from the cells. Hepatocytes from clofibrate-pretreated mice were much less susceptible to acetaminophen than cells from vehicle-treated controls. However, the extent of glutathione depletion during exposure to acetaminophen was similar in both cell types, as were rates of excretion of the product of glutathione-mediated detoxication of acetaminophen's quinoneimine metabolite, 3-glutathionyl-acetaminophen. The glutathione-replenishing ability of clofibrate-pretreated cells after a brief exposure to diethyl maleate also resembled that of control cells. More importantly, prior depletion of glutathione by diethyl maleate did not abolish the resistance of clofibrate-pretreated cells to acetaminophen. Taken together, these findings indicate that although glutathione-dependent pathways may contribute to hepatoprotection during peroxisome proliferation, the resistance phenomenon is not due exclusively to this mechanism.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="5e49375a9b9df1749dcffab825ab067b" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":39513368,"asset_id":17446906,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/39513368/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="17446906"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="17446906"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 17446906; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=17446906]").text(description); $(".js-view-count[data-work-id=17446906]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 17446906; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='17446906']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "5e49375a9b9df1749dcffab825ab067b" } } $('.js-work-strip[data-work-id=17446906]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":17446906,"title":"Clofibrate-Induced in Vitro Hepatoprotection against Acetaminophen Is Not Due to Altered Glutathione Homeostasis","internal_url":"https://www.academia.edu/17446906/Clofibrate_Induced_in_Vitro_Hepatoprotection_against_Acetaminophen_Is_Not_Due_to_Altered_Glutathione_Homeostasis","owner_id":37187764,"coauthors_can_edit":true,"owner":{"id":37187764,"first_name":"Philip","middle_initials":null,"last_name":"Burcham","page_name":"PhilipBurcham","domain_name":"independent","created_at":"2015-10-28T21:31:21.614-07:00","display_name":"Philip Burcham","url":"https://independent.academia.edu/PhilipBurcham"},"attachments":[{"id":39513368,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/39513368/thumbnails/1.jpg","file_name":"220.pdf","download_url":"https://www.academia.edu/attachments/39513368/download_file","bulk_download_file_name":"Clofibrate_Induced_in_Vitro_Hepatoprotec.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/39513368/220-libre.pdf?1446093227=\u0026response-content-disposition=attachment%3B+filename%3DClofibrate_Induced_in_Vitro_Hepatoprotec.pdf\u0026Expires=1740224218\u0026Signature=Q376CVGc3~70US68Xj7-n~U8i1-1dbbCUTdGhi6mgkb-YfUFV1VZ-UBcmamF8YtqFjFzgnO-DKiTjxy5dEj1ZfbGCliE4ilhk34TmWxR9ZSrK2fh2J6FldhCDZpMhmD~qLbhUPcmGF1ECqqucJsCceeqOTLnM5qRLXxzAHbWEQtrkY3hwRwwcNgodnWVj4Zs2nV6V6SEZ~sUOWhpDpAEuS8qlvLzfKNXVXWMG3SeDG73HvVuH-He~-89mZqt6xk2wbSHunwU0fJilEQ4K3NrQ1KHSMZCAWX6TKiw1He128u~VuEicK24oTCdDGnXIo886qcMc-olZvr0UJXhmR846Q__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="8552535"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/8552535/Michael_addition_of_acrolein_to_lysinyl_and_N_terminal_residues_of_a_model_peptide_targets_for_cytoprotective_hydrazino_drugs"><img alt="Research paper thumbnail of Michael addition of acrolein to lysinyl and N-terminal residues of a model peptide: targets for cytoprotective hydrazino drugs" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/8552535/Michael_addition_of_acrolein_to_lysinyl_and_N_terminal_residues_of_a_model_peptide_targets_for_cytoprotective_hydrazino_drugs">Michael addition of acrolein to lysinyl and N-terminal residues of a model peptide: targets for cytoprotective hydrazino drugs</a></div><div class="wp-workCard_item wp-workCard--coauthors"><span>by </span><span><a class="" data-click-track="profile-work-strip-authors" href="https://independent.academia.edu/SimonPyke">Simon Pyke</a> and <a class="" data-click-track="profile-work-strip-authors" href="https://independent.academia.edu/PhilipBurcham">Philip Burcham</a></span></div><div class="wp-workCard_item"><span>Rapid Communications in Mass Spectrometry</span><span>, 2007</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The antihypertensive drug hydralazine blocks acrolein-mediated toxicity by trapping both free ald...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The antihypertensive drug hydralazine blocks acrolein-mediated toxicity by trapping both free aldehyde- and acrolein-adducted proteins, with the latter property more closely related to cytoprotection in cellular models. Here we report the identification of products from ‘protein adduct-trapping’ reactions using electrospray ionisation mass spectrometry (ESI-MS). Reaction of a 13-residue peptide containing a single lysine with acrolein for 30 min generated ions corresponding to mono- and bis-Michael-adducted peptides. An ion corresponding to a cyclic species formed from bis-adducted lysine was conspicuous at later times (60, 180 min). Tandem mass spectrometric (MS/MS) analysis revealed Michael adduction also occurred on the N-terminus, with a novel N-terminal (3-formyl-3,4-dehydropiperidino) species formed on this residue. Addition of hydralazine to acrolein-adducted peptides generated a diverse range of hydrazones that were also characterised by MS/MS analysis. The results confirm that mass spectrometry is a powerful tool for characterising the reactions of noxious electrophiles with biological macromolecules. Copyright © 2007 John Wiley & Sons, Ltd.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="8552535"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="8552535"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 8552535; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=8552535]").text(description); $(".js-view-count[data-work-id=8552535]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 8552535; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='8552535']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); 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</script> <div class="js-work-strip profile--work_container" data-work-id="8552524"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/8552524/Reactivity_of_hydrazinophthalazine_drugs_with_the_lipid_peroxidation_products_acrolein_and_crotonaldehyde"><img alt="Research paper thumbnail of Reactivity of hydrazinophthalazine drugs with the lipid peroxidation products acrolein and crotonaldehyde" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/8552524/Reactivity_of_hydrazinophthalazine_drugs_with_the_lipid_peroxidation_products_acrolein_and_crotonaldehyde">Reactivity of hydrazinophthalazine drugs with the lipid peroxidation products acrolein and crotonaldehyde</a></div><div class="wp-workCard_item wp-workCard--coauthors"><span>by </span><span><a class="" data-click-track="profile-work-strip-authors" href="https://independent.academia.edu/SimonPyke">Simon Pyke</a> and <a class="" data-click-track="profile-work-strip-authors" href="https://independent.academia.edu/PhilipBurcham">Philip Burcham</a></span></div><div class="wp-workCard_item"><span>Organic & Biomolecular Chemistry</span><span>, 2004</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The nucleophilic drug hydralazine strongly inhibits cell toxicity mediated by acrolein, a short c...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The nucleophilic drug hydralazine strongly inhibits cell toxicity mediated by acrolein, a short chain 2-alkenal formed during lipid peroxidation. We here report the chemistry of acrolein-trapping by hydralazine, and show that together with its structural analogue dihydralazine, it also readily traps crotonaldehyde. Isolable reaction products included (1E)-acrylaldehyde phthalazin-1-ylhydrazone (E-APH), (1Z)-acrylaldehyde phthalazin-1-ylhydrazone (Z-APH), (1E,2E)-but-2-enal phthalazin-1-ylhydrazone (E-BPH) and (1Z,2E)-but-2-enal phthalazin-1-ylhydrazone (Z-BPH). Concentration-dependent formation of (1E)-acrylaldehyde phthalazin-1-ylhydrazone was observed in the culture media of cells co-exposed to hydralazine and the acrolein precursor allyl alcohol. These aldehyde-sequestering properties of hydrazinophthalazine drugs may contribute to the protection they provide against 2-alkenal-mediated toxicity.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="8552524"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="8552524"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 8552524; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=8552524]").text(description); $(".js-view-count[data-work-id=8552524]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 8552524; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='8552524']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=8552524]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":8552524,"title":"Reactivity of hydrazinophthalazine drugs with the lipid peroxidation products acrolein and crotonaldehyde","internal_url":"https://www.academia.edu/8552524/Reactivity_of_hydrazinophthalazine_drugs_with_the_lipid_peroxidation_products_acrolein_and_crotonaldehyde","owner_id":17601503,"coauthors_can_edit":true,"owner":{"id":17601503,"first_name":"Simon","middle_initials":null,"last_name":"Pyke","page_name":"SimonPyke","domain_name":"independent","created_at":"2014-09-29T08:58:16.374-07:00","display_name":"Simon Pyke","url":"https://independent.academia.edu/SimonPyke"},"attachments":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="17446905"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/17446905/Carbonyl_Scavenging_Drugs_and_Protection_Against_Carbonyl_Stress_Associated_Cell_Injury"><img alt="Research paper thumbnail of Carbonyl-Scavenging Drugs & Protection Against Carbonyl Stress-Associated Cell Injury" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/17446905/Carbonyl_Scavenging_Drugs_and_Protection_Against_Carbonyl_Stress_Associated_Cell_Injury">Carbonyl-Scavenging Drugs & Protection Against Carbonyl Stress-Associated Cell Injury</a></div><div class="wp-workCard_item"><span>Mini-Reviews in Medicinal Chemistry</span><span>, 2008</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">This mini-review highlights the chemical and cytoprotective properties of various hydralazine ana...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">This mini-review highlights the chemical and cytoprotective properties of various hydralazine analogues that block the induction of cell death by acrolein, a highly toxic contributor to &amp;quot;carbonyl stress&amp;quot; during a diverse range of human diseases. Recent work on the action of hydralazine against various carbonyl-mediated pathologies is also reviewed.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="17446905"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="17446905"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 17446905; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=17446905]").text(description); $(".js-view-count[data-work-id=17446905]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 17446905; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='17446905']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=17446905]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":17446905,"title":"Carbonyl-Scavenging Drugs \u0026 Protection Against Carbonyl Stress-Associated Cell Injury","internal_url":"https://www.academia.edu/17446905/Carbonyl_Scavenging_Drugs_and_Protection_Against_Carbonyl_Stress_Associated_Cell_Injury","owner_id":37187764,"coauthors_can_edit":true,"owner":{"id":37187764,"first_name":"Philip","middle_initials":null,"last_name":"Burcham","page_name":"PhilipBurcham","domain_name":"independent","created_at":"2015-10-28T21:31:21.614-07:00","display_name":"Philip Burcham","url":"https://independent.academia.edu/PhilipBurcham"},"attachments":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="17446904"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/17446904/Role_of_cytochrome_P450_3A_in_the_metabolism_of_mefloquine_in_human_and_animal_hepatocytes"><img alt="Research paper thumbnail of Role of cytochrome P450 3A in the metabolism of mefloquine in human and animal hepatocytes" class="work-thumbnail" src="https://attachments.academia-assets.com/42259355/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/17446904/Role_of_cytochrome_P450_3A_in_the_metabolism_of_mefloquine_in_human_and_animal_hepatocytes">Role of cytochrome P450 3A in the metabolism of mefloquine in human and animal hepatocytes</a></div><div class="wp-workCard_item"><span>Life Sciences</span><span>, 2000</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">ABSTRACT We studied mefloquine metabolism in cells and microsomes isolated from human and animal ...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">ABSTRACT We studied mefloquine metabolism in cells and microsomes isolated from human and animal (monkey, dog, rat) livers. In both hepatocytes and microsomes, mefloquine underwent conversion to two major metabolites, carboxymefloquine and hydroxymefloquine. In human cells and microsomes these metabolites only were formed, as already demonstrated in vivo, while in other species several unidentified metabolites were also detected. After a 48 hr incubation with human and rat hepatocytes, metabolites accounted for 55-65% of the initial drug concentration, whereas in monkey and dog hepatocytes, mefloquine was entirely metabolized after 15 and 39 hrs, respectively. The consumption of mefloquine was less extensive in microsomes, and unchanged drug represented 60% (monkey) to 85-100% (human, dog, rat) of the total radioactivity after 5 hr incubations. The involvement of the cytochrome P450 3A subfamily in mefloquine biotransformation was suggested by several lines of evidence. Firstly, mefloquine metabolism was strongly increased in hepatic microsomes from dexamethasone-pretreated rats, and also in human and rat hepatocytes after prior treatment with a cytochrome P450 3A inducer. Secondly, mefloquine biotransformation in rifampycin-induced human hepatocytes was inhibited in a concentration-dependent manner by the cytochrome P450 3A inhibitor ketoconazole and thirdly, a strong correlation was found between erythromycin-N-demethylase activity (mediated by cytochrome P450 3A) and mefloquine metabolism in human microsomes (r=0.81, P &amp;lt; 0.05, N=13). Collectively, these findings concerning the role of cytochrome P450 3A in mefloquine metabolism may have important in vivo consequences especially with regard to the choice of agents used in multidrug antimalarial regimens.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="7a1b06e57d6d1891f22fc9dd88524152" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":42259355,"asset_id":17446904,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/42259355/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="17446904"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="17446904"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 17446904; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=17446904]").text(description); $(".js-view-count[data-work-id=17446904]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 17446904; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='17446904']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "7a1b06e57d6d1891f22fc9dd88524152" } } $('.js-work-strip[data-work-id=17446904]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":17446904,"title":"Role of cytochrome P450 3A in the metabolism of mefloquine in human and animal hepatocytes","internal_url":"https://www.academia.edu/17446904/Role_of_cytochrome_P450_3A_in_the_metabolism_of_mefloquine_in_human_and_animal_hepatocytes","owner_id":37187764,"coauthors_can_edit":true,"owner":{"id":37187764,"first_name":"Philip","middle_initials":null,"last_name":"Burcham","page_name":"PhilipBurcham","domain_name":"independent","created_at":"2015-10-28T21:31:21.614-07:00","display_name":"Philip Burcham","url":"https://independent.academia.edu/PhilipBurcham"},"attachments":[{"id":42259355,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/42259355/thumbnails/1.jpg","file_name":"s0024-3205_2800_2900546-4.pdf20160206-1785-1vqoyig","download_url":"https://www.academia.edu/attachments/42259355/download_file","bulk_download_file_name":"Role_of_cytochrome_P450_3A_in_the_metabo.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/42259355/s0024-3205_2800_2900546-4-libre.pdf20160206-1785-1vqoyig?1454824280=\u0026response-content-disposition=attachment%3B+filename%3DRole_of_cytochrome_P450_3A_in_the_metabo.pdf\u0026Expires=1740224218\u0026Signature=aZf6E8T968yddLWbcUDAqKlVVPN6Gaz9gWUYQogejAOf-MSshCU~BYDzpJ9Q5J8rhrbDm0WCVwi0URhJOnc~b2KAlNGAVNNMwcoSrRn72aI2zF7IxYaq23UHt5ADVRnglrpaX066Ix5TBPZ7Khw2Z-BWgyYssSVwK2hiusCD5n8yR2X95Luc6ySBuiDOHbFzt8NdHjqGgwiU7pM2t2VqPa3EENTRLvJ1amjdN9-LrlqUlvChbI-XIQLnJnjQzK40f2~7J6T6N6t9OtC1ARnzgWbsTtWdBIVjfXhDM3Ibfhvz8m-3TOJoeOcMp6CaRDOVvYcQK0zfCYs~EsDHfUPRZQ__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="16347163"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/16347163/Cylindrospermopsin_Genotoxicity_and_Cytotoxicity_Role_Of_Cytochrome_P_450_and_Oxidative_Stress"><img alt="Research paper thumbnail of Cylindrospermopsin Genotoxicity and Cytotoxicity: Role Of Cytochrome P-450 and Oxidative Stress" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/16347163/Cylindrospermopsin_Genotoxicity_and_Cytotoxicity_Role_Of_Cytochrome_P_450_and_Oxidative_Stress">Cylindrospermopsin Genotoxicity and Cytotoxicity: Role Of Cytochrome P-450 and Oxidative Stress</a></div><div class="wp-workCard_item wp-workCard--coauthors"><span>by </span><span><a class="" data-click-track="profile-work-strip-authors" href="https://independent.academia.edu/FalconerIan">Ian Falconer</a>, <a class="" data-click-track="profile-work-strip-authors" href="https://independent.academia.edu/PhilipBurcham">Philip Burcham</a>, and <a class="" data-click-track="profile-work-strip-authors" href="https://uq.academia.edu/FrankFontaine">Frank Fontaine</a></span></div><div class="wp-workCard_item"><span>Journal of Toxicology and Environmental Health, Part A</span><span>, 2005</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Cylindrospermopsin (CYN) is a cyanobacterial toxin found in drinking-water sources world wide. It...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Cylindrospermopsin (CYN) is a cyanobacterial toxin found in drinking-water sources world wide. It was the likely cause of human poisonings in Australia and possibly Brazil. Although CYN itself is a potent protein synthesis inhibitor, its acute toxicity appears to be mediated by cytochrome p-450 (CYP450)-generated metabolites. CYN also induces genotoxic effects both in vitro and in vivo, and preliminary evidence suggests that tumors are generated by oral exposure to CYN. To understand the role of CYP450-activated CYN metabolites on in vitro genotoxicity, this study quantified the process in primary mouse hepatocytes using the COMET assay in both the presence and absence of CYP450 inhibitors known to block acute CYN cytotoxicity. CYN was cytotoxic at concentrations above 0.1 microM (EC50 = 0.5 microM) but produced significant increases in Comet tail length, area, and tail moment at 0.05 microM and above; hence genotoxicity is unlikely to be secondary to metabolic disruption due to toxicity. The CYP450 inhibitors omeprazole (100 microM) and SKF525A (50 microM) completely inhibited the genotoxicity induced by CYN. The toxin also inhibits production of glutathione (GSH), a finding confirmed in this study. This could potentiate cytotoxicity, and by implication genotoxicity, via reduced reactive oxygen species (ROS) quenching. The lipid peroxidation marker, malondialdehyde (MDA) was quantified in CYN-treated cells, and the effect of the reduced glutathione (GSSG) reductase (GSSG-rd.) inhibitor 1,3-bis(chloroethyl)-l-nitrosourea (BCNU) on both MDA production and lactate dehydrogenase (LDH) leakage was examined. MDA levels were not elevated by CYN treatment, and block of GSH regeneration by BCNU did not affect lipid peroxidation or cytotoxicity. It therefore seems likely that CYP450-derived metabolites are responsible for both the acute cytotoxicity and genotoxicity induced by CYN.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="16347163"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="16347163"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 16347163; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=16347163]").text(description); $(".js-view-count[data-work-id=16347163]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 16347163; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='16347163']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=16347163]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":16347163,"title":"Cylindrospermopsin Genotoxicity and Cytotoxicity: Role Of Cytochrome P-450 and Oxidative Stress","internal_url":"https://www.academia.edu/16347163/Cylindrospermopsin_Genotoxicity_and_Cytotoxicity_Role_Of_Cytochrome_P_450_and_Oxidative_Stress","owner_id":35468568,"coauthors_can_edit":true,"owner":{"id":35468568,"first_name":"Ian","middle_initials":null,"last_name":"Falconer","page_name":"FalconerIan","domain_name":"independent","created_at":"2015-09-30T23:44:41.729-07:00","display_name":"Ian Falconer","url":"https://independent.academia.edu/FalconerIan"},"attachments":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="17446903"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/17446903/Clofibrate_pretreatment_in_mice_confers_resistance_against_hepatic_lipid_peroxidation"><img alt="Research paper thumbnail of Clofibrate pretreatment in mice confers resistance against hepatic lipid peroxidation" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/17446903/Clofibrate_pretreatment_in_mice_confers_resistance_against_hepatic_lipid_peroxidation">Clofibrate pretreatment in mice confers resistance against hepatic lipid peroxidation</a></div><div class="wp-workCard_item"><span>Journal of Biochemical and Molecular Toxicology</span><span>, 2000</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Pretreatment with peroxisome proliferators protects mice against various hepatotoxicants. Since o...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Pretreatment with peroxisome proliferators protects mice against various hepatotoxicants. Since our previous work suggested that the hepatoprotection may involve an increased ability to cope with oxidative stress, the present work directly addressed this possibility. Several observations indicated a heightened defense against oxidative stress accompanies the hepatoprotection produced by clofibrate. Firstly, the carbonyl content of hepatic proteins from clofibrate-pretreated mice was 40% lower than those from vehicle-treated controls. Secondly, liver homogenates from clofibrate-pretreated mice produced less thiobarbituric acid reactive substances upon incubation under aerobic conditions or exposure to ferrous sulfate. This effect was not due to lower levels of peroxidation-prone polyunsaturated fatty acids in clofibrate-treated livers. Thirdly, in vitro experiments indicated that the antioxidant factor in liver homogenates from clofibrate-pretreated mice was not glutathione. Rather, since it was inactivated by proteases and heat treatment, we concluded that a protein is involved. Collectively, our results suggest that a resistance to lipid peroxidation develops in mouse liver during exposure to clofibrate. The identity of the putative antioxidant protein and its contribution to the protection against liver toxicity observed in this and other laboratories awaits future investigation.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="17446903"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="17446903"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 17446903; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=17446903]").text(description); $(".js-view-count[data-work-id=17446903]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 17446903; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='17446903']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=17446903]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":17446903,"title":"Clofibrate pretreatment in mice confers resistance against hepatic lipid peroxidation","internal_url":"https://www.academia.edu/17446903/Clofibrate_pretreatment_in_mice_confers_resistance_against_hepatic_lipid_peroxidation","owner_id":37187764,"coauthors_can_edit":true,"owner":{"id":37187764,"first_name":"Philip","middle_initials":null,"last_name":"Burcham","page_name":"PhilipBurcham","domain_name":"independent","created_at":"2015-10-28T21:31:21.614-07:00","display_name":"Philip Burcham","url":"https://independent.academia.edu/PhilipBurcham"},"attachments":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="17446902"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/17446902/Extensive_protein_carbonylation_precedes_acrolein_mediated_cell_death_in_mouse_hepatocytes"><img alt="Research paper thumbnail of Extensive protein carbonylation precedes acrolein-mediated cell death in mouse hepatocytes" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/17446902/Extensive_protein_carbonylation_precedes_acrolein_mediated_cell_death_in_mouse_hepatocytes">Extensive protein carbonylation precedes acrolein-mediated cell death in mouse hepatocytes</a></div><div class="wp-workCard_item"><span>Journal of Biochemical and Molecular Toxicology</span><span>, 2001</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Allyl alcohol hepatotoxicity is mediated by an alcohol dehydrogenase-derived biotranformation pro...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Allyl alcohol hepatotoxicity is mediated by an alcohol dehydrogenase-derived biotranformation product, acrolein. This highly reactive alpha,beta-unsaturated aldehyde readily alkylates model proteins in vitro, forming, among other products, Michael addition adducts that possess a free carbonyl group. Whether such damage accompanies acrolein-mediated toxicity in cells is unknown. In this work we established that allyl alcohol toxicity in mouse hepatocytes involves extensive carbonylation of a wide range of proteins, and that the severity of such damage to a subset of 18-50 kDa proteins closely correlated with the degree of cell death. In addition to abolishing cytotoxicity and glutathione depletion, the alcohol dehydrogenase inhibitor 4-methyl pyrazole strongly attenuated protein carbonylation. Conversely, cyanamide, an aldehyde dehydrogenase inhibitor, enhanced cytotoxicity and protein carbonylation. Since protein carbonylation clearly preceded the loss of membrane integrity, it may be associated with the toxic process leading to cell death.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="17446902"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="17446902"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 17446902; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=17446902]").text(description); $(".js-view-count[data-work-id=17446902]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 17446902; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='17446902']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=17446902]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":17446902,"title":"Extensive protein carbonylation precedes acrolein-mediated cell death in mouse hepatocytes","internal_url":"https://www.academia.edu/17446902/Extensive_protein_carbonylation_precedes_acrolein_mediated_cell_death_in_mouse_hepatocytes","owner_id":37187764,"coauthors_can_edit":true,"owner":{"id":37187764,"first_name":"Philip","middle_initials":null,"last_name":"Burcham","page_name":"PhilipBurcham","domain_name":"independent","created_at":"2015-10-28T21:31:21.614-07:00","display_name":"Philip Burcham","url":"https://independent.academia.edu/PhilipBurcham"},"attachments":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="16347158"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/16347158/Cylindrospermopsin_induced_protein_synthesis_inhibition_and_its_dissociation_from_acute_toxicity_in_mouse_hepatocytes"><img alt="Research paper thumbnail of Cylindrospermopsin-induced protein synthesis inhibition and its dissociation from acute toxicity in mouse hepatocytes" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/16347158/Cylindrospermopsin_induced_protein_synthesis_inhibition_and_its_dissociation_from_acute_toxicity_in_mouse_hepatocytes">Cylindrospermopsin-induced protein synthesis inhibition and its dissociation from acute toxicity in mouse hepatocytes</a></div><div class="wp-workCard_item wp-workCard--coauthors"><span>by </span><span><a class="" data-click-track="profile-work-strip-authors" href="https://independent.academia.edu/FalconerIan">Ian Falconer</a> and <a class="" data-click-track="profile-work-strip-authors" href="https://independent.academia.edu/PhilipBurcham">Philip Burcham</a></span></div><div class="wp-workCard_item"><span>Environmental Toxicology</span><span>, 2003</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The toxicology of the cyanobacterial alkaloid cylindrospermopsin (CYN), a potent inhibitor of pro...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The toxicology of the cyanobacterial alkaloid cylindrospermopsin (CYN), a potent inhibitor of protein synthesis, appears complex and is not well understood. In exposed mice the liver is the main target for the toxic effects of CYN. In this study primary mouse hepatocyte cultures were used to investigate the mechanisms involved in CYN toxicity. The results show that 1-5 microM CYN caused significant concentration-dependent cytotoxicity (52%-82% cell death) at 18 h. Protein synthesis inhibition was a sensitive, early indicator of cellular responses to CYN. Following removal of the toxin, the inhibition of protein synthesis could not be reversed, showing behavior similar to that of the irreversible inhibitor emetine. In contrast to the LDH leakage, protein synthesis was maximally inhibited by 0.5 microM CYN. No protein synthesis occurred over 4-18 h at or above this concentration. Inhibition of cytochrome P450 (CYP450) activity with 50 microM proadifen or 50 microM ketoconazole diminished the toxicity of CYN but not the effects on protein synthesis. These findings imply a dissociation of the two events and implicate the involvement of CYP450-derived metabolites in the toxicity process, but not in the impairment of protein synthesis. Thus, the total abolition of protein synthesis may exaggerate the metabolite effects but cannot be considered a primary cause of cell death in hepatocytes over an acute time frame. In cell types deficient in CYP450 enzymes, protein synthesis inhibition may play a more crucial role in the development of cytotoxicity.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="16347158"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="16347158"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 16347158; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=16347158]").text(description); 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</script> </div><div class="profile--tab_content_container js-tab-pane tab-pane" data-section-id="3872888" id="papers"><div class="js-work-strip profile--work_container" data-work-id="124940232"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/124940232/Faculty_of_1000_evaluation_for_Pharmacometabonomic_identification_of_a_significant_host_microbiome_metabolic_interaction_affecting_human_drug_metabolism"><img alt="Research paper thumbnail of Faculty of 1000 evaluation for Pharmacometabonomic identification of a significant host-microbiome metabolic interaction affecting human drug metabolism" class="work-thumbnail" src="https://attachments.academia-assets.com/119072427/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/124940232/Faculty_of_1000_evaluation_for_Pharmacometabonomic_identification_of_a_significant_host_microbiome_metabolic_interaction_affecting_human_drug_metabolism">Faculty of 1000 evaluation for Pharmacometabonomic identification of a significant host-microbiome metabolic interaction affecting human drug metabolism</a></div><div class="wp-workCard_item"><span>F1000 - Post-publication peer review of the biomedical literature</span><span>, 2009</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="a3dba70f79a0355c3d8ebff1d81079f7" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":119072427,"asset_id":124940232,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/119072427/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="124940232"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="124940232"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 124940232; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=124940232]").text(description); $(".js-view-count[data-work-id=124940232]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 124940232; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='124940232']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="120657145"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/120657145/Hydralazine_Inhibits_Rapid_Acrolein_Induced_Protein_Oligomerization_Role_of_Aldehyde_Scavenging_and_Adduct_Trapping_in_Cross_Link_Blocking_and_Cytoprotection"><img alt="Research paper thumbnail of Hydralazine Inhibits Rapid Acrolein-Induced Protein Oligomerization: Role of Aldehyde Scavenging and Adduct Trapping in Cross-Link Blocking and Cytoprotection" class="work-thumbnail" src="https://attachments.academia-assets.com/115737399/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/120657145/Hydralazine_Inhibits_Rapid_Acrolein_Induced_Protein_Oligomerization_Role_of_Aldehyde_Scavenging_and_Adduct_Trapping_in_Cross_Link_Blocking_and_Cytoprotection">Hydralazine Inhibits Rapid Acrolein-Induced Protein Oligomerization: Role of Aldehyde Scavenging and Adduct Trapping in Cross-Link Blocking and Cytoprotection</a></div><div class="wp-workCard_item"><span>Molecular Pharmacology</span><span>, 2005</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Hydralazine strongly suppresses the toxicity of acrolein, a reactive aldehyde that contributes to...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Hydralazine strongly suppresses the toxicity of acrolein, a reactive aldehyde that contributes to numerous health disorders. At least two mechanisms may underlie the cytoprotection, both of which involve the nucleophilic hydrazine possessed by hydralazine. Under the simplest scenario, hydralazine directly scavenges free acrolein, decreasing intracellular acrolein availability and thereby suppressing macromolecular adduction. In a second "adduct-trapping" mechanism, the drug forms hydrazones with acrolein-derived Michael adducts in cell proteins, preventing secondary reactions of adducted proteins that may trigger cell death. To identify the most important mechanism, we explored these two pathways in mouse hepatocytes poisoned with the acrolein precursor allyl alcohol. Intense concentration-dependent adduct-trapping in cell proteins accompanied the suppression of toxicity by hydralazine. However, protective concentrations of hydralazine did not alter extracellular free acrolein levels, cellular glutathione loss or protein carbonylation, suggesting the cytoprotection is not due to minimization of intracellular acrolein availability. To explore ways whereby adduct-trapping might confer cytoprotection, the effect of hydralazine on acrolein-induced protein cross-linking was examined. Using bovine pancreas ribonuclease A as a model protein, acrolein caused rapid time-and concentration-dependent cross-linking, with dimerized protein detectable within 45 min of commencing protein modification. Lysine adduction in monomeric protein preceded the appearance of oligomers, while reductive methylation of protein amine groups abolished both adduction and oligomerization. Hydralazine inhibited cross-linking if added 30 min after commencing acrolein exposure but was ineffective if added after a 90 min delay. Adduct-trapping closely accompanied the inhibition of This article has not been copyedited and formatted. The final version may differ from this version.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="d936e0574caa2a6bfd14611c49127f79" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":115737399,"asset_id":120657145,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/115737399/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="120657145"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="120657145"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 120657145; 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="115243773"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/115243773/Faculty_of_1000_evaluation_for_Assessment_of_Protein_Binding_of_5_Hydroxythalidomide_Bioactivated_in_Humanized_Mice_with_Human_P450_3A_Chromosome_or_Hepatocytes_by_Two_Dimensional_Electrophoresis_Accelerator_Mass_Spectrometry"><img alt="Research paper thumbnail of Faculty of 1000 evaluation for Assessment of Protein Binding of 5-Hydroxythalidomide Bioactivated in Humanized Mice with Human P450 3A-Chromosome or Hepatocytes by Two-Dimensional Electrophoresis/Accelerator Mass Spectrometry" class="work-thumbnail" src="https://attachments.academia-assets.com/111707902/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/115243773/Faculty_of_1000_evaluation_for_Assessment_of_Protein_Binding_of_5_Hydroxythalidomide_Bioactivated_in_Humanized_Mice_with_Human_P450_3A_Chromosome_or_Hepatocytes_by_Two_Dimensional_Electrophoresis_Accelerator_Mass_Spectrometry">Faculty of 1000 evaluation for Assessment of Protein Binding of 5-Hydroxythalidomide Bioactivated in Humanized Mice with Human P450 3A-Chromosome or Hepatocytes by Two-Dimensional Electrophoresis/Accelerator Mass Spectrometry</a></div><div class="wp-workCard_item"><span>F1000 - Post-publication peer review of the biomedical literature</span><span>, 2017</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Bioactivation of 5-hydroxy-[carbonyl-14 C]thalidomide, a known metabolite of thalidomide, by huma...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Bioactivation of 5-hydroxy-[carbonyl-14 C]thalidomide, a known metabolite of thalidomide, by human artificial or native cytochrome P450 3A enzymes, and nonspecific binding in livers of mice was assessed using two-dimensional electrophoresis combined with accelerator mass spectrometry. The apparent major target proteins were liver microsomal cytochrome c oxidase subunit 6B1 and ATP synthase subunit α in mice containing humanized P450 3A genes or transplanted humanized liver. Liver cytosolic retinal dehydrogenase 1 and glutathione transferase *</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="10770a95e07353d0805ad664ff09413b" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":111707902,"asset_id":115243773,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/111707902/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="115243773"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="115243773"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 115243773; 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="106827461"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/106827461/Faculty_of_1000_evaluation_for_Aristolochic_acid_associated_urothelial_cancer_in_Taiwan"><img alt="Research paper thumbnail of Faculty of 1000 evaluation for Aristolochic acid-associated urothelial cancer in Taiwan" class="work-thumbnail" src="https://attachments.academia-assets.com/105806826/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/106827461/Faculty_of_1000_evaluation_for_Aristolochic_acid_associated_urothelial_cancer_in_Taiwan">Faculty of 1000 evaluation for Aristolochic acid-associated urothelial cancer in Taiwan</a></div><div class="wp-workCard_item"><span>F1000 - Post-publication peer review of the biomedical literature</span><span>, 2012</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="8eec22ce0b93fa04db1671f19b325dbe" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":105806826,"asset_id":106827461,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/105806826/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="106827461"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="106827461"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 106827461; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=106827461]").text(description); $(".js-view-count[data-work-id=106827461]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 106827461; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='106827461']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="50087456"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/50087456/Differences_in_Lysine_Adduction_by_Acrolein_and_Methyl_Vinyl_Ketone_Implications_for_Cytotoxicity_in_Cultured_Hepatocytes"><img alt="Research paper thumbnail of Differences in Lysine Adduction by Acrolein and Methyl Vinyl Ketone: Implications for Cytotoxicity in Cultured Hepatocytes" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/50087456/Differences_in_Lysine_Adduction_by_Acrolein_and_Methyl_Vinyl_Ketone_Implications_for_Cytotoxicity_in_Cultured_Hepatocytes">Differences in Lysine Adduction by Acrolein and Methyl Vinyl Ketone: Implications for Cytotoxicity in Cultured Hepatocytes</a></div><div class="wp-workCard_item"><span>Chemical Research in Toxicology</span><span>, 2005</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Acrolein is a highly toxic environmental pollutant that readily alkylates the epsilon-amino group...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Acrolein is a highly toxic environmental pollutant that readily alkylates the epsilon-amino group of lysine residues in proteins. In model systems, such chemistry involves sequential addition of two acrolein molecules to a given nitrogen, forming bis-Michael-adducted species that undergo aldol condensation and dehydration to form Nepsilon-(3-formyl-3,4-dehydropiperidino)lysine. Whether this ability to form cyclic adducts participates in the toxicity of acrolein is unknown. To address this issue, we compared the chemistry of protein adduction by acrolein to that of its close structural analogue methyl vinyl ketone, expecting that the alpha-methyl group would hinder the intramolecular cyclization of any bis-adducted species formed by methyl vinyl ketone. Both acrolein and methyl vinyl ketone displayed comparable protein carbonylating activity during in vitro studies with the model protein bovine serum albumin, confirming the alpha,beta,-unsaturated bond of both compounds is an efficient Michael acceptor for protein nucleophiles. However, differences in adduction chemistry became apparent during the use of electrospray ionization-MS to monitor reaction products in a lysine-containing peptide after modification by each compound. For example, although a Schiff base adduct was detected following reaction of the peptide with acrolein, an analogous species was not formed by methyl vinyl ketone. Furthermore, while ions corresponding to mono- and bis-Michael adducts were detected at the N-terminus and lysine residues following peptide modification by both carbonyls, only acrolein modification generated ions attributable to cyclic adducts. Despite these differences in adduction chemistry, in mouse hepatocytes, the two compounds exhibited very comparable abilities to induce rapid, concentration-dependent cell death as well as protein carbonylation. These findings suggest that the acute toxicity of short-chain alpha,beta-unsaturated carbonyl compounds involves their ability to form acyclic Michael addition adducts rather than Schiff conjugates or heterocyclic adducts.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="50087456"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="50087456"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 50087456; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=50087456]").text(description); $(".js-view-count[data-work-id=50087456]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 50087456; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='50087456']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); 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</script> <div class="js-work-strip profile--work_container" data-work-id="49772192"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/49772192/Reactivity_with_Tris_hydroxymethyl_aminomethane_Confounds_Immunodetection_of_Acrolein_Adducted_Proteins"><img alt="Research paper thumbnail of Reactivity with Tris(hydroxymethyl)aminomethane Confounds Immunodetection of Acrolein-Adducted Proteins" class="work-thumbnail" src="https://attachments.academia-assets.com/68011290/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/49772192/Reactivity_with_Tris_hydroxymethyl_aminomethane_Confounds_Immunodetection_of_Acrolein_Adducted_Proteins">Reactivity with Tris(hydroxymethyl)aminomethane Confounds Immunodetection of Acrolein-Adducted Proteins</a></div><div class="wp-workCard_item"><span>Chemical Research in Toxicology</span><span>, 2003</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The toxic R,-unsaturated aldehyde acrolein readily attacks proteins, generating adducts at cystei...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The toxic R,-unsaturated aldehyde acrolein readily attacks proteins, generating adducts at cysteine, histidine, and lysine residues. In this study, rabbit antiserum was raised against acrolein-modified keyhole limpet hemocyanin in the expectation that it would allow immunodetection of adducted proteins in biological samples. Using slot-blot and enzyme-linked immunosorbent assays, the antiserum detected acrolein-modified protein with high sensitivity and specificity. Adduct immunodetection was strongly inhibited by acrolein-modified polylysine but not polyhistidine. Efforts to develop a Western blotting method for detecting adducted proteins in cell lysates were hampered by irreproducible outcomes, evidently due to adduct instability during SDS-PAGE. Indeed, adducts generated via brief exposure of a model protein to acrolein displayed pH-and concentration-dependent instability to tris(hydroxymethyl)aminomethane (Tris), a nucleophilic buffer used in protein electrophoresis. The effect was most striking when Tris solutions were buffered to pH 8.0 and higher. In contrast, adducts formed during extended exposure to acrolein (g60 min) were completely stable to Tris. The time dependence of susceptibility raised the possibility that Tris interfered with specific steps in lysine modification, which involves stepwise Michael addition of two molecules of acrolein to the same residue, followed by condensation and dehydration to form a heterocyclic adduct, N-(3-formyl-3,4-dehydropiperidino)lysine. We hypothesize that carbonyl-retaining Michael adducts may react with Tris by forming imines with the primary amine of the buffer. Consistent with this idea, triethanolamine, a tertiary amine buffer unable to form imines, had no effect on acrolein-adducted protein. These effects of Tris may explain difficulties in the detection of acrolein-adducted proteins during conventional Western blotting procedures.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="abfb8857ae86c5981b28c859efcfcfc1" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":68011290,"asset_id":49772192,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/68011290/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="49772192"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="49772192"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 49772192; 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dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "abfb8857ae86c5981b28c859efcfcfc1" } } $('.js-work-strip[data-work-id=49772192]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":49772192,"title":"Reactivity with Tris(hydroxymethyl)aminomethane Confounds Immunodetection of Acrolein-Adducted Proteins","internal_url":"https://www.academia.edu/49772192/Reactivity_with_Tris_hydroxymethyl_aminomethane_Confounds_Immunodetection_of_Acrolein_Adducted_Proteins","owner_id":37187764,"coauthors_can_edit":true,"owner":{"id":37187764,"first_name":"Philip","middle_initials":null,"last_name":"Burcham","page_name":"PhilipBurcham","domain_name":"independent","created_at":"2015-10-28T21:31:21.614-07:00","display_name":"Philip Burcham","url":"https://independent.academia.edu/PhilipBurcham"},"attachments":[{"id":68011290,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/68011290/thumbnails/1.jpg","file_name":"tx034110620210711-8798-x68f0o.pdf","download_url":"https://www.academia.edu/attachments/68011290/download_file","bulk_download_file_name":"Reactivity_with_Tris_hydroxymethyl_amino.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/68011290/tx034110620210711-8798-x68f0o-libre.pdf?1626055644=\u0026response-content-disposition=attachment%3B+filename%3DReactivity_with_Tris_hydroxymethyl_amino.pdf\u0026Expires=1740224218\u0026Signature=TalV-I~KrObbvK4ynmIIRMYuA-uLdSoUqDI-6VbGD2KJj2dZFwth1QdyRx9IPWHSymweJtxBorTXCS9wwQ-4DmYGLLCBd524xgSaAVR5OlGEOxlsqE-HNWKvZcuVRxxmXejArDhBQ1PS7TqTpwyZQyLg-TpK9vq3DYiK6wBJrbxu3FSL0~iYJIPXDwhBDuMfHPnjghS6h~idUBkNPD7yj9MKxILmXSP0iOVMD3Z7dAu6ZO7riDtUuJ2qFf7ocsPAxiFbAcbgytKceTzkRlq9y~StompDwgAK~FL-ZyxkQb7Npqnnazrg4xudFR4g2EgrNt6HW9RbQ0BAYZys4Nz3zQ__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="46619372"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/46619372/Protein_Adduct_Trapping_by_Hydrazinophthalazine_Drugs_Mechanisms_of_Cytoprotection_Against_Acrolein_Mediated_Toxicity"><img alt="Research paper thumbnail of Protein Adduct-Trapping by Hydrazinophthalazine Drugs: Mechanisms of Cytoprotection Against Acrolein-Mediated Toxicity" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/46619372/Protein_Adduct_Trapping_by_Hydrazinophthalazine_Drugs_Mechanisms_of_Cytoprotection_Against_Acrolein_Mediated_Toxicity">Protein Adduct-Trapping by Hydrazinophthalazine Drugs: Mechanisms of Cytoprotection Against Acrolein-Mediated Toxicity</a></div><div class="wp-workCard_item"><span>Molecular Pharmacology</span><span>, 2004</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="46619372"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="46619372"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 46619372; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=46619372]").text(description); $(".js-view-count[data-work-id=46619372]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 46619372; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='46619372']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=46619372]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":46619372,"title":"Protein Adduct-Trapping by Hydrazinophthalazine Drugs: Mechanisms of Cytoprotection Against Acrolein-Mediated Toxicity","internal_url":"https://www.academia.edu/46619372/Protein_Adduct_Trapping_by_Hydrazinophthalazine_Drugs_Mechanisms_of_Cytoprotection_Against_Acrolein_Mediated_Toxicity","owner_id":37187764,"coauthors_can_edit":true,"owner":{"id":37187764,"first_name":"Philip","middle_initials":null,"last_name":"Burcham","page_name":"PhilipBurcham","domain_name":"independent","created_at":"2015-10-28T21:31:21.614-07:00","display_name":"Philip Burcham","url":"https://independent.academia.edu/PhilipBurcham"},"attachments":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="17446909"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/17446909/Influenza_A_infection_attenuates_relaxation_responses_of_mouse_tracheal_smooth_muscle_evoked_by_acrolein"><img alt="Research paper thumbnail of Influenza A infection attenuates relaxation responses of mouse tracheal smooth muscle evoked by acrolein" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/17446909/Influenza_A_infection_attenuates_relaxation_responses_of_mouse_tracheal_smooth_muscle_evoked_by_acrolein">Influenza A infection attenuates relaxation responses of mouse tracheal smooth muscle evoked by acrolein</a></div><div class="wp-workCard_item"><span>Biochemical pharmacology</span><span>, Jan 15, 2015</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The airway epithelium is an important source of relaxant mediators, and damage to the epithelium ...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The airway epithelium is an important source of relaxant mediators, and damage to the epithelium caused by respiratory tract viruses may contribute to airway hyperreactivity. The aim of this study was to determine whether influenza A-induced epithelial damage would modulate relaxation responses evoked by acrolein, a toxic and prevalent component of smoke. Male BALB/c mice were inoculated intranasally with influenza A/PR-8/34 (VIRUS-infected) or allantoic fluid (SHAM-infected). On day 4 post-inoculation, isometric tension recording studies were conducted on carbachol pre-contracted tracheal segments isolated from VIRUS and SHAM mice. Relaxant responses to acrolein (30μM) were markedly smaller in VIRUS segments compared to SHAM segments (2±1% relaxation vs. 28±5%, n=14, p&lt;0.01). Similarly, relaxation responses of VIRUS segments to the neuropeptide substance P (SP) were greatly attenuated (1±1% vs. 47±6% evoked by 1nM SP, n=14, p&lt;0.001). Consistent with epithelial damage, PGE2 re...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="17446909"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="17446909"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 17446909; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=17446909]").text(description); $(".js-view-count[data-work-id=17446909]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 17446909; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='17446909']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=17446909]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":17446909,"title":"Influenza A infection attenuates relaxation responses of mouse tracheal smooth muscle evoked by acrolein","internal_url":"https://www.academia.edu/17446909/Influenza_A_infection_attenuates_relaxation_responses_of_mouse_tracheal_smooth_muscle_evoked_by_acrolein","owner_id":37187764,"coauthors_can_edit":true,"owner":{"id":37187764,"first_name":"Philip","middle_initials":null,"last_name":"Burcham","page_name":"PhilipBurcham","domain_name":"independent","created_at":"2015-10-28T21:31:21.614-07:00","display_name":"Philip Burcham","url":"https://independent.academia.edu/PhilipBurcham"},"attachments":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="17446908"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/17446908/Optimisation_of_the_comet_genotoxicity_assay_in_freshly_isolated_murine_hepatocytes_detection_of_strong_in_vitro_DNA_damaging_properties_for_styrene"><img alt="Research paper thumbnail of Optimisation of the comet genotoxicity assay in freshly isolated murine hepatocytes: detection of strong in vitro DNA damaging properties for styrene" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/17446908/Optimisation_of_the_comet_genotoxicity_assay_in_freshly_isolated_murine_hepatocytes_detection_of_strong_in_vitro_DNA_damaging_properties_for_styrene">Optimisation of the comet genotoxicity assay in freshly isolated murine hepatocytes: detection of strong in vitro DNA damaging properties for styrene</a></div><div class="wp-workCard_item"><span>Toxicology in Vitro</span><span>, 2004</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">While the comet assay is used to detect DNA damage in isolated cells following exposure to chemic...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">While the comet assay is used to detect DNA damage in isolated cells following exposure to chemicals in vitro, few publications report the use of the procedure in liver cells isolated from mice. Our initial efforts to use the assay to assess DNA damage in mouse hepatocytes maintained on collagen-coated dishes were hampered by high levels of baseline damage in</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="17446908"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="17446908"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 17446908; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=17446908]").text(description); $(".js-view-count[data-work-id=17446908]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 17446908; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='17446908']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=17446908]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":17446908,"title":"Optimisation of the comet genotoxicity assay in freshly isolated murine hepatocytes: detection of strong in vitro DNA damaging properties for styrene","internal_url":"https://www.academia.edu/17446908/Optimisation_of_the_comet_genotoxicity_assay_in_freshly_isolated_murine_hepatocytes_detection_of_strong_in_vitro_DNA_damaging_properties_for_styrene","owner_id":37187764,"coauthors_can_edit":true,"owner":{"id":37187764,"first_name":"Philip","middle_initials":null,"last_name":"Burcham","page_name":"PhilipBurcham","domain_name":"independent","created_at":"2015-10-28T21:31:21.614-07:00","display_name":"Philip Burcham","url":"https://independent.academia.edu/PhilipBurcham"},"attachments":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="17446907"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/17446907/UDP_glucuronosyltransferase_dependent_bioactivation_of_clofibric_acid_to_a_DNA_damaging_intermediate_in_mouse_hepatocytes"><img alt="Research paper thumbnail of UDP-glucuronosyltransferase-dependent bioactivation of clofibric acid to a DNA-damaging intermediate in mouse hepatocytes" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/17446907/UDP_glucuronosyltransferase_dependent_bioactivation_of_clofibric_acid_to_a_DNA_damaging_intermediate_in_mouse_hepatocytes">UDP-glucuronosyltransferase-dependent bioactivation of clofibric acid to a DNA-damaging intermediate in mouse hepatocytes</a></div><div class="wp-workCard_item"><span>Chemico-biological Interactions</span><span>, 2003</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Glucuronidation of a number of carboxyl-containing drugs generates reactive acyl glucuronide meta...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Glucuronidation of a number of carboxyl-containing drugs generates reactive acyl glucuronide metabolites. These electrophilic species alkylate cell proteins and may be implicated in the pathogenesis of a number of toxic syndromes seen in patients receiving the parent aglycones. Whether acyl glucuronides also attack nuclear DNA is unknown, although the acyl glucuronide formed from clofibric acid was recently found to decrease</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="17446907"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="17446907"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 17446907; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=17446907]").text(description); $(".js-view-count[data-work-id=17446907]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 17446907; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='17446907']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); 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</script> <div class="js-work-strip profile--work_container" data-work-id="8552502"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/8552502/Aldehyde_sequestering_drugs_tools_for_studying_protein_damage_by_lipid_peroxidation_products"><img alt="Research paper thumbnail of Aldehyde-sequestering drugs: tools for studying protein damage by lipid peroxidation products" class="work-thumbnail" src="https://attachments.academia-assets.com/48057497/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/8552502/Aldehyde_sequestering_drugs_tools_for_studying_protein_damage_by_lipid_peroxidation_products">Aldehyde-sequestering drugs: tools for studying protein damage by lipid peroxidation products</a></div><div class="wp-workCard_item wp-workCard--coauthors"><span>by </span><span><a class="" data-click-track="profile-work-strip-authors" href="https://independent.academia.edu/SimonPyke">Simon Pyke</a>, <a class="" data-click-track="profile-work-strip-authors" href="https://uq.academia.edu/FrankFontaine">Frank Fontaine</a>, and <a class="" data-click-track="profile-work-strip-authors" href="https://independent.academia.edu/PhilipBurcham">Philip Burcham</a></span></div><div class="wp-workCard_item"><span>Toxicology</span><span>, 2002</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Elevated levels of reactive a,b-unsaturated aldehydes (e.g. malondialdehyde, 4-hydroxynonenal and...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Elevated levels of reactive a,b-unsaturated aldehydes (e.g. malondialdehyde, 4-hydroxynonenal and acrolein) in the affected tissues of various degenerative conditions suggest these substances are active propagators of the disease process. One experimental approach to attenuating damage by these intermediates employs 'aldehyde-sequestering drugs' as sacrificial nucleophiles, thereby sparing cell macromolecules and perhaps slowing disease progression. Drugs with demonstrated trapping activity toward lipid-derived aldehydes include various amine compounds such as aminoguanidine, carnosine and pyridoxamine. We have focused on identifying scavengers of acrolein, perhaps the most toxic aldehyde formed during lipid peroxidation cascades. Various phthalazine compounds (hydralazine and dihydralazine) were found to trap acrolein readily, forming hydrazone derivatives in a rapid Schiff-type reaction. These compounds strongly protect against acrolein-mediated toxicity in isolated hepatocytes.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="69898b0f43c0c2fcb7772c3589cfb8ac" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":48057497,"asset_id":8552502,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/48057497/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="8552502"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="8552502"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 8552502; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=8552502]").text(description); $(".js-view-count[data-work-id=8552502]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 8552502; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='8552502']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "69898b0f43c0c2fcb7772c3589cfb8ac" } } $('.js-work-strip[data-work-id=8552502]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":8552502,"title":"Aldehyde-sequestering drugs: tools for studying protein damage by lipid peroxidation products","internal_url":"https://www.academia.edu/8552502/Aldehyde_sequestering_drugs_tools_for_studying_protein_damage_by_lipid_peroxidation_products","owner_id":17601503,"coauthors_can_edit":true,"owner":{"id":17601503,"first_name":"Simon","middle_initials":null,"last_name":"Pyke","page_name":"SimonPyke","domain_name":"independent","created_at":"2014-09-29T08:58:16.374-07:00","display_name":"Simon Pyke","url":"https://independent.academia.edu/SimonPyke"},"attachments":[{"id":48057497,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/48057497/thumbnails/1.jpg","file_name":"s0300-483x_2802_2900287-120160814-13132-1k4wcvv.pdf","download_url":"https://www.academia.edu/attachments/48057497/download_file","bulk_download_file_name":"Aldehyde_sequestering_drugs_tools_for_st.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/48057497/s0300-483x_2802_2900287-120160814-13132-1k4wcvv-libre.pdf?1471239482=\u0026response-content-disposition=attachment%3B+filename%3DAldehyde_sequestering_drugs_tools_for_st.pdf\u0026Expires=1740220298\u0026Signature=AYwlMYughGOAbSqDdl6rw~-t-kzTtha0sm0Mzkv0-28aMPqlsCkpcDFYEIBPJLrMaaQu~d~UZcQkV4mwbVkIVWcp4JZrnXD5P~MiMZrZVA4rv6AeKJrcqm2sZC8zkU8sV7Of~d4Ywrcpdvt9n05dwuaA8bSjENY9l7cD7MBoBE7bV6PpYY7FPTvOmh52RFv2TWFDxWA7zQ9ZFS~uw6HbpgXgfOuVLQRWUg2Yj6H-vNLCsfRdnG-waKso8Biwk3a4h2OlJJtzhSXC5awVUe8PUWcu3PkfL8fJsROo6OqzOxyFY-g8UhF8NiDR3GVZXwjaBCfnD~y-edPMpycHwOqtDA__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="17446906"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/17446906/Clofibrate_Induced_in_Vitro_Hepatoprotection_against_Acetaminophen_Is_Not_Due_to_Altered_Glutathione_Homeostasis"><img alt="Research paper thumbnail of Clofibrate-Induced in Vitro Hepatoprotection against Acetaminophen Is Not Due to Altered Glutathione Homeostasis" class="work-thumbnail" src="https://attachments.academia-assets.com/39513368/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/17446906/Clofibrate_Induced_in_Vitro_Hepatoprotection_against_Acetaminophen_Is_Not_Due_to_Altered_Glutathione_Homeostasis">Clofibrate-Induced in Vitro Hepatoprotection against Acetaminophen Is Not Due to Altered Glutathione Homeostasis</a></div><div class="wp-workCard_item"><span>Toxicological Sciences</span><span>, 2000</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Prior induction of peroxisome proliferation protects mice against the in vivo hepatotoxicity of a...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Prior induction of peroxisome proliferation protects mice against the in vivo hepatotoxicity of acetaminophen and various other bioactivation-dependent toxicants. The mechanisms underlying such chemoresistance are poorly understood, although they have been suggested to involve alterations in glutathione homeostasis. To clarify the role of glutathione in this phenomenon, we isolated hepatocytes from mice in which hepatic peroxisome proliferation had been induced with clofibrate. The cells were incubated with a range of acetaminophen concentrations and the extent of cell killing after up to 8 h was assessed by measuring lactate dehydrogenase leakage from the cells. Hepatocytes from clofibrate-pretreated mice were much less susceptible to acetaminophen than cells from vehicle-treated controls. However, the extent of glutathione depletion during exposure to acetaminophen was similar in both cell types, as were rates of excretion of the product of glutathione-mediated detoxication of acetaminophen's quinoneimine metabolite, 3-glutathionyl-acetaminophen. The glutathione-replenishing ability of clofibrate-pretreated cells after a brief exposure to diethyl maleate also resembled that of control cells. More importantly, prior depletion of glutathione by diethyl maleate did not abolish the resistance of clofibrate-pretreated cells to acetaminophen. Taken together, these findings indicate that although glutathione-dependent pathways may contribute to hepatoprotection during peroxisome proliferation, the resistance phenomenon is not due exclusively to this mechanism.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="5e49375a9b9df1749dcffab825ab067b" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":39513368,"asset_id":17446906,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/39513368/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="17446906"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="17446906"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 17446906; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=17446906]").text(description); $(".js-view-count[data-work-id=17446906]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 17446906; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='17446906']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "5e49375a9b9df1749dcffab825ab067b" } } $('.js-work-strip[data-work-id=17446906]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":17446906,"title":"Clofibrate-Induced in Vitro Hepatoprotection against Acetaminophen Is Not Due to Altered Glutathione Homeostasis","internal_url":"https://www.academia.edu/17446906/Clofibrate_Induced_in_Vitro_Hepatoprotection_against_Acetaminophen_Is_Not_Due_to_Altered_Glutathione_Homeostasis","owner_id":37187764,"coauthors_can_edit":true,"owner":{"id":37187764,"first_name":"Philip","middle_initials":null,"last_name":"Burcham","page_name":"PhilipBurcham","domain_name":"independent","created_at":"2015-10-28T21:31:21.614-07:00","display_name":"Philip Burcham","url":"https://independent.academia.edu/PhilipBurcham"},"attachments":[{"id":39513368,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/39513368/thumbnails/1.jpg","file_name":"220.pdf","download_url":"https://www.academia.edu/attachments/39513368/download_file","bulk_download_file_name":"Clofibrate_Induced_in_Vitro_Hepatoprotec.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/39513368/220-libre.pdf?1446093227=\u0026response-content-disposition=attachment%3B+filename%3DClofibrate_Induced_in_Vitro_Hepatoprotec.pdf\u0026Expires=1740224218\u0026Signature=Q376CVGc3~70US68Xj7-n~U8i1-1dbbCUTdGhi6mgkb-YfUFV1VZ-UBcmamF8YtqFjFzgnO-DKiTjxy5dEj1ZfbGCliE4ilhk34TmWxR9ZSrK2fh2J6FldhCDZpMhmD~qLbhUPcmGF1ECqqucJsCceeqOTLnM5qRLXxzAHbWEQtrkY3hwRwwcNgodnWVj4Zs2nV6V6SEZ~sUOWhpDpAEuS8qlvLzfKNXVXWMG3SeDG73HvVuH-He~-89mZqt6xk2wbSHunwU0fJilEQ4K3NrQ1KHSMZCAWX6TKiw1He128u~VuEicK24oTCdDGnXIo886qcMc-olZvr0UJXhmR846Q__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="8552535"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/8552535/Michael_addition_of_acrolein_to_lysinyl_and_N_terminal_residues_of_a_model_peptide_targets_for_cytoprotective_hydrazino_drugs"><img alt="Research paper thumbnail of Michael addition of acrolein to lysinyl and N-terminal residues of a model peptide: targets for cytoprotective hydrazino drugs" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/8552535/Michael_addition_of_acrolein_to_lysinyl_and_N_terminal_residues_of_a_model_peptide_targets_for_cytoprotective_hydrazino_drugs">Michael addition of acrolein to lysinyl and N-terminal residues of a model peptide: targets for cytoprotective hydrazino drugs</a></div><div class="wp-workCard_item wp-workCard--coauthors"><span>by </span><span><a class="" data-click-track="profile-work-strip-authors" href="https://independent.academia.edu/SimonPyke">Simon Pyke</a> and <a class="" data-click-track="profile-work-strip-authors" href="https://independent.academia.edu/PhilipBurcham">Philip Burcham</a></span></div><div class="wp-workCard_item"><span>Rapid Communications in Mass Spectrometry</span><span>, 2007</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The antihypertensive drug hydralazine blocks acrolein-mediated toxicity by trapping both free ald...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The antihypertensive drug hydralazine blocks acrolein-mediated toxicity by trapping both free aldehyde- and acrolein-adducted proteins, with the latter property more closely related to cytoprotection in cellular models. Here we report the identification of products from ‘protein adduct-trapping’ reactions using electrospray ionisation mass spectrometry (ESI-MS). Reaction of a 13-residue peptide containing a single lysine with acrolein for 30 min generated ions corresponding to mono- and bis-Michael-adducted peptides. An ion corresponding to a cyclic species formed from bis-adducted lysine was conspicuous at later times (60, 180 min). Tandem mass spectrometric (MS/MS) analysis revealed Michael adduction also occurred on the N-terminus, with a novel N-terminal (3-formyl-3,4-dehydropiperidino) species formed on this residue. Addition of hydralazine to acrolein-adducted peptides generated a diverse range of hydrazones that were also characterised by MS/MS analysis. The results confirm that mass spectrometry is a powerful tool for characterising the reactions of noxious electrophiles with biological macromolecules. Copyright © 2007 John Wiley & Sons, Ltd.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="8552535"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="8552535"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 8552535; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=8552535]").text(description); $(".js-view-count[data-work-id=8552535]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 8552535; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='8552535']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); 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</script> <div class="js-work-strip profile--work_container" data-work-id="8552524"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/8552524/Reactivity_of_hydrazinophthalazine_drugs_with_the_lipid_peroxidation_products_acrolein_and_crotonaldehyde"><img alt="Research paper thumbnail of Reactivity of hydrazinophthalazine drugs with the lipid peroxidation products acrolein and crotonaldehyde" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/8552524/Reactivity_of_hydrazinophthalazine_drugs_with_the_lipid_peroxidation_products_acrolein_and_crotonaldehyde">Reactivity of hydrazinophthalazine drugs with the lipid peroxidation products acrolein and crotonaldehyde</a></div><div class="wp-workCard_item wp-workCard--coauthors"><span>by </span><span><a class="" data-click-track="profile-work-strip-authors" href="https://independent.academia.edu/SimonPyke">Simon Pyke</a> and <a class="" data-click-track="profile-work-strip-authors" href="https://independent.academia.edu/PhilipBurcham">Philip Burcham</a></span></div><div class="wp-workCard_item"><span>Organic & Biomolecular Chemistry</span><span>, 2004</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The nucleophilic drug hydralazine strongly inhibits cell toxicity mediated by acrolein, a short c...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The nucleophilic drug hydralazine strongly inhibits cell toxicity mediated by acrolein, a short chain 2-alkenal formed during lipid peroxidation. We here report the chemistry of acrolein-trapping by hydralazine, and show that together with its structural analogue dihydralazine, it also readily traps crotonaldehyde. Isolable reaction products included (1E)-acrylaldehyde phthalazin-1-ylhydrazone (E-APH), (1Z)-acrylaldehyde phthalazin-1-ylhydrazone (Z-APH), (1E,2E)-but-2-enal phthalazin-1-ylhydrazone (E-BPH) and (1Z,2E)-but-2-enal phthalazin-1-ylhydrazone (Z-BPH). Concentration-dependent formation of (1E)-acrylaldehyde phthalazin-1-ylhydrazone was observed in the culture media of cells co-exposed to hydralazine and the acrolein precursor allyl alcohol. These aldehyde-sequestering properties of hydrazinophthalazine drugs may contribute to the protection they provide against 2-alkenal-mediated toxicity.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="8552524"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="8552524"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 8552524; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=8552524]").text(description); $(".js-view-count[data-work-id=8552524]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 8552524; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='8552524']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=8552524]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":8552524,"title":"Reactivity of hydrazinophthalazine drugs with the lipid peroxidation products acrolein and crotonaldehyde","internal_url":"https://www.academia.edu/8552524/Reactivity_of_hydrazinophthalazine_drugs_with_the_lipid_peroxidation_products_acrolein_and_crotonaldehyde","owner_id":17601503,"coauthors_can_edit":true,"owner":{"id":17601503,"first_name":"Simon","middle_initials":null,"last_name":"Pyke","page_name":"SimonPyke","domain_name":"independent","created_at":"2014-09-29T08:58:16.374-07:00","display_name":"Simon Pyke","url":"https://independent.academia.edu/SimonPyke"},"attachments":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="17446905"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/17446905/Carbonyl_Scavenging_Drugs_and_Protection_Against_Carbonyl_Stress_Associated_Cell_Injury"><img alt="Research paper thumbnail of Carbonyl-Scavenging Drugs & Protection Against Carbonyl Stress-Associated Cell Injury" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/17446905/Carbonyl_Scavenging_Drugs_and_Protection_Against_Carbonyl_Stress_Associated_Cell_Injury">Carbonyl-Scavenging Drugs & Protection Against Carbonyl Stress-Associated Cell Injury</a></div><div class="wp-workCard_item"><span>Mini-Reviews in Medicinal Chemistry</span><span>, 2008</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">This mini-review highlights the chemical and cytoprotective properties of various hydralazine ana...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">This mini-review highlights the chemical and cytoprotective properties of various hydralazine analogues that block the induction of cell death by acrolein, a highly toxic contributor to &amp;quot;carbonyl stress&amp;quot; during a diverse range of human diseases. Recent work on the action of hydralazine against various carbonyl-mediated pathologies is also reviewed.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="17446905"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="17446905"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 17446905; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=17446905]").text(description); $(".js-view-count[data-work-id=17446905]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 17446905; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='17446905']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=17446905]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":17446905,"title":"Carbonyl-Scavenging Drugs \u0026 Protection Against Carbonyl Stress-Associated Cell Injury","internal_url":"https://www.academia.edu/17446905/Carbonyl_Scavenging_Drugs_and_Protection_Against_Carbonyl_Stress_Associated_Cell_Injury","owner_id":37187764,"coauthors_can_edit":true,"owner":{"id":37187764,"first_name":"Philip","middle_initials":null,"last_name":"Burcham","page_name":"PhilipBurcham","domain_name":"independent","created_at":"2015-10-28T21:31:21.614-07:00","display_name":"Philip Burcham","url":"https://independent.academia.edu/PhilipBurcham"},"attachments":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="17446904"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/17446904/Role_of_cytochrome_P450_3A_in_the_metabolism_of_mefloquine_in_human_and_animal_hepatocytes"><img alt="Research paper thumbnail of Role of cytochrome P450 3A in the metabolism of mefloquine in human and animal hepatocytes" class="work-thumbnail" src="https://attachments.academia-assets.com/42259355/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/17446904/Role_of_cytochrome_P450_3A_in_the_metabolism_of_mefloquine_in_human_and_animal_hepatocytes">Role of cytochrome P450 3A in the metabolism of mefloquine in human and animal hepatocytes</a></div><div class="wp-workCard_item"><span>Life Sciences</span><span>, 2000</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">ABSTRACT We studied mefloquine metabolism in cells and microsomes isolated from human and animal ...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">ABSTRACT We studied mefloquine metabolism in cells and microsomes isolated from human and animal (monkey, dog, rat) livers. In both hepatocytes and microsomes, mefloquine underwent conversion to two major metabolites, carboxymefloquine and hydroxymefloquine. In human cells and microsomes these metabolites only were formed, as already demonstrated in vivo, while in other species several unidentified metabolites were also detected. After a 48 hr incubation with human and rat hepatocytes, metabolites accounted for 55-65% of the initial drug concentration, whereas in monkey and dog hepatocytes, mefloquine was entirely metabolized after 15 and 39 hrs, respectively. The consumption of mefloquine was less extensive in microsomes, and unchanged drug represented 60% (monkey) to 85-100% (human, dog, rat) of the total radioactivity after 5 hr incubations. The involvement of the cytochrome P450 3A subfamily in mefloquine biotransformation was suggested by several lines of evidence. Firstly, mefloquine metabolism was strongly increased in hepatic microsomes from dexamethasone-pretreated rats, and also in human and rat hepatocytes after prior treatment with a cytochrome P450 3A inducer. Secondly, mefloquine biotransformation in rifampycin-induced human hepatocytes was inhibited in a concentration-dependent manner by the cytochrome P450 3A inhibitor ketoconazole and thirdly, a strong correlation was found between erythromycin-N-demethylase activity (mediated by cytochrome P450 3A) and mefloquine metabolism in human microsomes (r=0.81, P &amp;lt; 0.05, N=13). Collectively, these findings concerning the role of cytochrome P450 3A in mefloquine metabolism may have important in vivo consequences especially with regard to the choice of agents used in multidrug antimalarial regimens.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="7a1b06e57d6d1891f22fc9dd88524152" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":42259355,"asset_id":17446904,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/42259355/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="17446904"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="17446904"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 17446904; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=17446904]").text(description); $(".js-view-count[data-work-id=17446904]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 17446904; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='17446904']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "7a1b06e57d6d1891f22fc9dd88524152" } } $('.js-work-strip[data-work-id=17446904]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":17446904,"title":"Role of cytochrome P450 3A in the metabolism of mefloquine in human and animal hepatocytes","internal_url":"https://www.academia.edu/17446904/Role_of_cytochrome_P450_3A_in_the_metabolism_of_mefloquine_in_human_and_animal_hepatocytes","owner_id":37187764,"coauthors_can_edit":true,"owner":{"id":37187764,"first_name":"Philip","middle_initials":null,"last_name":"Burcham","page_name":"PhilipBurcham","domain_name":"independent","created_at":"2015-10-28T21:31:21.614-07:00","display_name":"Philip Burcham","url":"https://independent.academia.edu/PhilipBurcham"},"attachments":[{"id":42259355,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/42259355/thumbnails/1.jpg","file_name":"s0024-3205_2800_2900546-4.pdf20160206-1785-1vqoyig","download_url":"https://www.academia.edu/attachments/42259355/download_file","bulk_download_file_name":"Role_of_cytochrome_P450_3A_in_the_metabo.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/42259355/s0024-3205_2800_2900546-4-libre.pdf20160206-1785-1vqoyig?1454824280=\u0026response-content-disposition=attachment%3B+filename%3DRole_of_cytochrome_P450_3A_in_the_metabo.pdf\u0026Expires=1740224218\u0026Signature=aZf6E8T968yddLWbcUDAqKlVVPN6Gaz9gWUYQogejAOf-MSshCU~BYDzpJ9Q5J8rhrbDm0WCVwi0URhJOnc~b2KAlNGAVNNMwcoSrRn72aI2zF7IxYaq23UHt5ADVRnglrpaX066Ix5TBPZ7Khw2Z-BWgyYssSVwK2hiusCD5n8yR2X95Luc6ySBuiDOHbFzt8NdHjqGgwiU7pM2t2VqPa3EENTRLvJ1amjdN9-LrlqUlvChbI-XIQLnJnjQzK40f2~7J6T6N6t9OtC1ARnzgWbsTtWdBIVjfXhDM3Ibfhvz8m-3TOJoeOcMp6CaRDOVvYcQK0zfCYs~EsDHfUPRZQ__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="16347163"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/16347163/Cylindrospermopsin_Genotoxicity_and_Cytotoxicity_Role_Of_Cytochrome_P_450_and_Oxidative_Stress"><img alt="Research paper thumbnail of Cylindrospermopsin Genotoxicity and Cytotoxicity: Role Of Cytochrome P-450 and Oxidative Stress" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/16347163/Cylindrospermopsin_Genotoxicity_and_Cytotoxicity_Role_Of_Cytochrome_P_450_and_Oxidative_Stress">Cylindrospermopsin Genotoxicity and Cytotoxicity: Role Of Cytochrome P-450 and Oxidative Stress</a></div><div class="wp-workCard_item wp-workCard--coauthors"><span>by </span><span><a class="" data-click-track="profile-work-strip-authors" href="https://independent.academia.edu/FalconerIan">Ian Falconer</a>, <a class="" data-click-track="profile-work-strip-authors" href="https://independent.academia.edu/PhilipBurcham">Philip Burcham</a>, and <a class="" data-click-track="profile-work-strip-authors" href="https://uq.academia.edu/FrankFontaine">Frank Fontaine</a></span></div><div class="wp-workCard_item"><span>Journal of Toxicology and Environmental Health, Part A</span><span>, 2005</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Cylindrospermopsin (CYN) is a cyanobacterial toxin found in drinking-water sources world wide. It...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Cylindrospermopsin (CYN) is a cyanobacterial toxin found in drinking-water sources world wide. It was the likely cause of human poisonings in Australia and possibly Brazil. Although CYN itself is a potent protein synthesis inhibitor, its acute toxicity appears to be mediated by cytochrome p-450 (CYP450)-generated metabolites. CYN also induces genotoxic effects both in vitro and in vivo, and preliminary evidence suggests that tumors are generated by oral exposure to CYN. To understand the role of CYP450-activated CYN metabolites on in vitro genotoxicity, this study quantified the process in primary mouse hepatocytes using the COMET assay in both the presence and absence of CYP450 inhibitors known to block acute CYN cytotoxicity. CYN was cytotoxic at concentrations above 0.1 microM (EC50 = 0.5 microM) but produced significant increases in Comet tail length, area, and tail moment at 0.05 microM and above; hence genotoxicity is unlikely to be secondary to metabolic disruption due to toxicity. The CYP450 inhibitors omeprazole (100 microM) and SKF525A (50 microM) completely inhibited the genotoxicity induced by CYN. The toxin also inhibits production of glutathione (GSH), a finding confirmed in this study. This could potentiate cytotoxicity, and by implication genotoxicity, via reduced reactive oxygen species (ROS) quenching. The lipid peroxidation marker, malondialdehyde (MDA) was quantified in CYN-treated cells, and the effect of the reduced glutathione (GSSG) reductase (GSSG-rd.) inhibitor 1,3-bis(chloroethyl)-l-nitrosourea (BCNU) on both MDA production and lactate dehydrogenase (LDH) leakage was examined. MDA levels were not elevated by CYN treatment, and block of GSH regeneration by BCNU did not affect lipid peroxidation or cytotoxicity. It therefore seems likely that CYP450-derived metabolites are responsible for both the acute cytotoxicity and genotoxicity induced by CYN.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="16347163"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="16347163"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 16347163; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=16347163]").text(description); $(".js-view-count[data-work-id=16347163]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 16347163; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='16347163']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=16347163]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":16347163,"title":"Cylindrospermopsin Genotoxicity and Cytotoxicity: Role Of Cytochrome P-450 and Oxidative Stress","internal_url":"https://www.academia.edu/16347163/Cylindrospermopsin_Genotoxicity_and_Cytotoxicity_Role_Of_Cytochrome_P_450_and_Oxidative_Stress","owner_id":35468568,"coauthors_can_edit":true,"owner":{"id":35468568,"first_name":"Ian","middle_initials":null,"last_name":"Falconer","page_name":"FalconerIan","domain_name":"independent","created_at":"2015-09-30T23:44:41.729-07:00","display_name":"Ian Falconer","url":"https://independent.academia.edu/FalconerIan"},"attachments":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="17446903"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/17446903/Clofibrate_pretreatment_in_mice_confers_resistance_against_hepatic_lipid_peroxidation"><img alt="Research paper thumbnail of Clofibrate pretreatment in mice confers resistance against hepatic lipid peroxidation" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/17446903/Clofibrate_pretreatment_in_mice_confers_resistance_against_hepatic_lipid_peroxidation">Clofibrate pretreatment in mice confers resistance against hepatic lipid peroxidation</a></div><div class="wp-workCard_item"><span>Journal of Biochemical and Molecular Toxicology</span><span>, 2000</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Pretreatment with peroxisome proliferators protects mice against various hepatotoxicants. Since o...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Pretreatment with peroxisome proliferators protects mice against various hepatotoxicants. Since our previous work suggested that the hepatoprotection may involve an increased ability to cope with oxidative stress, the present work directly addressed this possibility. Several observations indicated a heightened defense against oxidative stress accompanies the hepatoprotection produced by clofibrate. Firstly, the carbonyl content of hepatic proteins from clofibrate-pretreated mice was 40% lower than those from vehicle-treated controls. Secondly, liver homogenates from clofibrate-pretreated mice produced less thiobarbituric acid reactive substances upon incubation under aerobic conditions or exposure to ferrous sulfate. This effect was not due to lower levels of peroxidation-prone polyunsaturated fatty acids in clofibrate-treated livers. Thirdly, in vitro experiments indicated that the antioxidant factor in liver homogenates from clofibrate-pretreated mice was not glutathione. Rather, since it was inactivated by proteases and heat treatment, we concluded that a protein is involved. Collectively, our results suggest that a resistance to lipid peroxidation develops in mouse liver during exposure to clofibrate. The identity of the putative antioxidant protein and its contribution to the protection against liver toxicity observed in this and other laboratories awaits future investigation.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="17446903"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="17446903"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 17446903; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=17446903]").text(description); $(".js-view-count[data-work-id=17446903]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 17446903; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='17446903']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=17446903]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":17446903,"title":"Clofibrate pretreatment in mice confers resistance against hepatic lipid peroxidation","internal_url":"https://www.academia.edu/17446903/Clofibrate_pretreatment_in_mice_confers_resistance_against_hepatic_lipid_peroxidation","owner_id":37187764,"coauthors_can_edit":true,"owner":{"id":37187764,"first_name":"Philip","middle_initials":null,"last_name":"Burcham","page_name":"PhilipBurcham","domain_name":"independent","created_at":"2015-10-28T21:31:21.614-07:00","display_name":"Philip Burcham","url":"https://independent.academia.edu/PhilipBurcham"},"attachments":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="17446902"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/17446902/Extensive_protein_carbonylation_precedes_acrolein_mediated_cell_death_in_mouse_hepatocytes"><img alt="Research paper thumbnail of Extensive protein carbonylation precedes acrolein-mediated cell death in mouse hepatocytes" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/17446902/Extensive_protein_carbonylation_precedes_acrolein_mediated_cell_death_in_mouse_hepatocytes">Extensive protein carbonylation precedes acrolein-mediated cell death in mouse hepatocytes</a></div><div class="wp-workCard_item"><span>Journal of Biochemical and Molecular Toxicology</span><span>, 2001</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Allyl alcohol hepatotoxicity is mediated by an alcohol dehydrogenase-derived biotranformation pro...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Allyl alcohol hepatotoxicity is mediated by an alcohol dehydrogenase-derived biotranformation product, acrolein. This highly reactive alpha,beta-unsaturated aldehyde readily alkylates model proteins in vitro, forming, among other products, Michael addition adducts that possess a free carbonyl group. Whether such damage accompanies acrolein-mediated toxicity in cells is unknown. In this work we established that allyl alcohol toxicity in mouse hepatocytes involves extensive carbonylation of a wide range of proteins, and that the severity of such damage to a subset of 18-50 kDa proteins closely correlated with the degree of cell death. In addition to abolishing cytotoxicity and glutathione depletion, the alcohol dehydrogenase inhibitor 4-methyl pyrazole strongly attenuated protein carbonylation. Conversely, cyanamide, an aldehyde dehydrogenase inhibitor, enhanced cytotoxicity and protein carbonylation. Since protein carbonylation clearly preceded the loss of membrane integrity, it may be associated with the toxic process leading to cell death.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="17446902"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="17446902"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 17446902; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=17446902]").text(description); $(".js-view-count[data-work-id=17446902]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 17446902; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='17446902']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=17446902]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":17446902,"title":"Extensive protein carbonylation precedes acrolein-mediated cell death in mouse hepatocytes","internal_url":"https://www.academia.edu/17446902/Extensive_protein_carbonylation_precedes_acrolein_mediated_cell_death_in_mouse_hepatocytes","owner_id":37187764,"coauthors_can_edit":true,"owner":{"id":37187764,"first_name":"Philip","middle_initials":null,"last_name":"Burcham","page_name":"PhilipBurcham","domain_name":"independent","created_at":"2015-10-28T21:31:21.614-07:00","display_name":"Philip Burcham","url":"https://independent.academia.edu/PhilipBurcham"},"attachments":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="16347158"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/16347158/Cylindrospermopsin_induced_protein_synthesis_inhibition_and_its_dissociation_from_acute_toxicity_in_mouse_hepatocytes"><img alt="Research paper thumbnail of Cylindrospermopsin-induced protein synthesis inhibition and its dissociation from acute toxicity in mouse hepatocytes" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/16347158/Cylindrospermopsin_induced_protein_synthesis_inhibition_and_its_dissociation_from_acute_toxicity_in_mouse_hepatocytes">Cylindrospermopsin-induced protein synthesis inhibition and its dissociation from acute toxicity in mouse hepatocytes</a></div><div class="wp-workCard_item wp-workCard--coauthors"><span>by </span><span><a class="" data-click-track="profile-work-strip-authors" href="https://independent.academia.edu/FalconerIan">Ian Falconer</a> and <a class="" data-click-track="profile-work-strip-authors" href="https://independent.academia.edu/PhilipBurcham">Philip Burcham</a></span></div><div class="wp-workCard_item"><span>Environmental Toxicology</span><span>, 2003</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The toxicology of the cyanobacterial alkaloid cylindrospermopsin (CYN), a potent inhibitor of pro...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The toxicology of the cyanobacterial alkaloid cylindrospermopsin (CYN), a potent inhibitor of protein synthesis, appears complex and is not well understood. In exposed mice the liver is the main target for the toxic effects of CYN. In this study primary mouse hepatocyte cultures were used to investigate the mechanisms involved in CYN toxicity. The results show that 1-5 microM CYN caused significant concentration-dependent cytotoxicity (52%-82% cell death) at 18 h. Protein synthesis inhibition was a sensitive, early indicator of cellular responses to CYN. Following removal of the toxin, the inhibition of protein synthesis could not be reversed, showing behavior similar to that of the irreversible inhibitor emetine. In contrast to the LDH leakage, protein synthesis was maximally inhibited by 0.5 microM CYN. No protein synthesis occurred over 4-18 h at or above this concentration. Inhibition of cytochrome P450 (CYP450) activity with 50 microM proadifen or 50 microM ketoconazole diminished the toxicity of CYN but not the effects on protein synthesis. These findings imply a dissociation of the two events and implicate the involvement of CYP450-derived metabolites in the toxicity process, but not in the impairment of protein synthesis. Thus, the total abolition of protein synthesis may exaggerate the metabolite effects but cannot be considered a primary cause of cell death in hepatocytes over an acute time frame. In cell types deficient in CYP450 enzymes, protein synthesis inhibition may play a more crucial role in the development of cytotoxicity.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="16347158"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="16347158"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 16347158; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=16347158]").text(description); $(".js-view-count[data-work-id=16347158]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 16347158; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='16347158']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=16347158]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":16347158,"title":"Cylindrospermopsin-induced protein synthesis inhibition and its dissociation from acute toxicity in mouse hepatocytes","internal_url":"https://www.academia.edu/16347158/Cylindrospermopsin_induced_protein_synthesis_inhibition_and_its_dissociation_from_acute_toxicity_in_mouse_hepatocytes","owner_id":35468568,"coauthors_can_edit":true,"owner":{"id":35468568,"first_name":"Ian","middle_initials":null,"last_name":"Falconer","page_name":"FalconerIan","domain_name":"independent","created_at":"2015-09-30T23:44:41.729-07:00","display_name":"Ian Falconer","url":"https://independent.academia.edu/FalconerIan"},"attachments":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> </div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/google_contacts-0dfb882d836b94dbcb4a2d123d6933fc9533eda5be911641f20b4eb428429600.js"], function() { // from javascript_helper.rb $('.js-google-connect-button').click(function(e) { e.preventDefault(); GoogleContacts.authorize_and_show_contacts(); Aedu.Dismissibles.recordClickthrough("WowProfileImportContactsPrompt"); }); $('.js-update-biography-button').click(function(e) { e.preventDefault(); Aedu.Dismissibles.recordClickthrough("UpdateUserBiographyPrompt"); $.ajax({ url: $r.api_v0_profiles_update_about_path({ subdomain_param: 'api', about: "", }), type: 'PUT', success: function(response) { location.reload(); } }); }); $('.js-work-creator-button').click(function (e) { e.preventDefault(); window.location = $r.upload_funnel_document_path({ source: encodeURIComponent(""), }); 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