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{"work":{"id":93214672,"created_at":"2022-12-18T23:10:21.750-08:00","from_world_paper_id":223205397,"updated_at":"2022-12-18T23:34:45.829-08:00","_data":{"publisher":"Wiley","publication_date":"2000,,","publication_name":"The FASEB Journal"},"document_type":"paper","pre_hit_view_count_baseline":null,"quality":"high","language":"en","title":"Melatonin but not vitamins C and E maintains glutathione homeostasis in t‐butyl hydroperoxide‐induced mitochondrial oxidative stress","broadcastable":false,"draft":null,"has_indexable_attachment":true,"indexable":true}}["work"]; window.loswp.workCoauthors = [34398486]; window.loswp.locale = "en"; window.loswp.countryCode = "SG"; window.loswp.cwvAbTestBucket = ""; window.loswp.designVariant = "ds_vanilla"; window.loswp.fullPageMobileSutdModalVariant = "control"; window.loswp.useOptimizedScribd4genScript = false; window.loginModal = {}; window.loginModal.appleClientId = 'edu.academia.applesignon';</script><script defer="" 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class="ds-related-content--heading">Related papers</h2><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="0" data-entity-id="4373542" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/4373542/Melatonin_protects_the_mitochondria_from_oxidative_damage_reducing_oxygen_consumption_membrane_potential_and_superoxide_anion_production">Melatonin protects the mitochondria from oxidative damage reducing oxygen consumption, membrane potential, and superoxide anion production</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="5348647" href="https://independent.academia.edu/FranciscoOrtiz2">Francisco Ortiz</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Journal of Pineal Research, 2009</p><p class="ds-related-work--abstract ds2-5-body-sm">Abstract: The role of melatonin in improving 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To date, however, the mechanism(s) involved are largely unknown. Using high-resolution respirometry, fluorometry and spectrophotometry we studied the effects of melatonin on normal mitochondrial functions. Mitochondria were recovered from mouse liver cells and incubated in vitro with melatonin at concentrations ranging from 1 nm to 1 mm. Melatonin decreased oxygen consumption concomitantly with its concentration, inhibited any increase in oxygen flux in the presence of an excess of ADP, reduced the membrane potential, and consequently inhibited the production of superoxide anion and hydrogen peroxide. At the same time it maintained the efficiency of oxidative phosphorylation and ATP synthesis while increasing the activity of the respiratory complexes (mainly complexes I, III, and IV). The effects of melatonin appeared to be due to its presence within the mitochondria, since kinetic experiments clearly showed its incorporation into these organelles. Our results support the hypothesis that melatonin, together with hormones such as triiodothyronine, participates in the physiological regulation of mitochondrial homeostasis.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Melatonin protects the mitochondria from oxidative damage reducing oxygen consumption, membrane potential, and superoxide anion production","attachmentId":49899279,"attachmentType":"pdf","work_url":"https://www.academia.edu/4373542/Melatonin_protects_the_mitochondria_from_oxidative_damage_reducing_oxygen_consumption_membrane_potential_and_superoxide_anion_production","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/4373542/Melatonin_protects_the_mitochondria_from_oxidative_damage_reducing_oxygen_consumption_membrane_potential_and_superoxide_anion_production"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="1" data-entity-id="18057178" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/18057178/Intracellular_Pro_oxidant_Activity_of_Melatonin_Deprives_U937_Cells_of_Reduced_Glutathione_without_Affecting_Glutathione_Peroxidase_Activity">Intracellular Pro-oxidant Activity of Melatonin Deprives U937 Cells of Reduced Glutathione without Affecting Glutathione Peroxidase Activity</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="38003947" href="https://independent.academia.edu/ClaudiaCerella">Claudia Cerella</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Annals of the New York Academy of Sciences, 2006</p><p class="ds-related-work--abstract ds2-5-body-sm">It was long believed that melatonin might counteract intracellular oxidative stress because it was shown to potentiate antioxidant endogenous defences, and to increase the activity of many antioxidant enzymes. However, it is now becoming evident that when radicals are measured within cells, melatonin increases, rather than decreasing, radical production. Herein we demonstrate a pro-oxidant effect of melatonin in U937 cells by showing an increase of intracellular oxidative species and a depletion of glutathione (GSH). The activity of glutathione peroxidase is not modified by melatonin treatment as it does occur in other experimental models.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Intracellular Pro-oxidant Activity of Melatonin Deprives U937 Cells of Reduced Glutathione without Affecting Glutathione Peroxidase Activity","attachmentId":39852766,"attachmentType":"pdf","work_url":"https://www.academia.edu/18057178/Intracellular_Pro_oxidant_Activity_of_Melatonin_Deprives_U937_Cells_of_Reduced_Glutathione_without_Affecting_Glutathione_Peroxidase_Activity","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/18057178/Intracellular_Pro_oxidant_Activity_of_Melatonin_Deprives_U937_Cells_of_Reduced_Glutathione_without_Affecting_Glutathione_Peroxidase_Activity"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="2" data-entity-id="99831139" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/99831139/A_proposed_mechanism_to_explain_the_stimulatory_effect_of_melatonin_on_antioxidative_enzymes">A proposed mechanism to explain the stimulatory effect of melatonin on antioxidative enzymes</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="6074201" href="https://independent.academia.edu/AnaCoto">Ana Coto</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Journal of Pineal Research, 2005</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"A proposed mechanism to explain the stimulatory effect of melatonin on antioxidative enzymes","attachmentId":100814966,"attachmentType":"pdf","work_url":"https://www.academia.edu/99831139/A_proposed_mechanism_to_explain_the_stimulatory_effect_of_melatonin_on_antioxidative_enzymes","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/99831139/A_proposed_mechanism_to_explain_the_stimulatory_effect_of_melatonin_on_antioxidative_enzymes"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="3" data-entity-id="15301648" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/15301648/A_review_of_the_evidence_supporting_melatonins_role_as_an_antioxidant">A review of the evidence supporting melatonin's role as an antioxidant</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="34398486" href="https://ugr.academia.edu/Dar%C3%ADoAcu%C3%B1acastroviejo">Darío Acuña-castroviejo</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Journal of Pineal Research, 1995</p><p class="ds-related-work--abstract ds2-5-body-sm">review of the evidence supporting melatonin's role as an antioxidant. J. Pineal Res. 1995;lS: 1-1 1.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"A review of the evidence supporting melatonin's role as an antioxidant","attachmentId":43351418,"attachmentType":"pdf","work_url":"https://www.academia.edu/15301648/A_review_of_the_evidence_supporting_melatonins_role_as_an_antioxidant","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/15301648/A_review_of_the_evidence_supporting_melatonins_role_as_an_antioxidant"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="4" data-entity-id="80422170" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/80422170/Melatonin_increases_the_activity_of_the_oxidative_phosphorylation_enzymes_and_the_production_of_ATP_in_rat_brain_and_liver_mitochondria">Melatonin increases the activity of the oxidative phosphorylation enzymes and the production of ATP in rat brain and liver mitochondria</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="51031805" href="https://uma.academia.edu/ManuelMac%C3%ADas">Manuel Macías</a></div><p class="ds-related-work--metadata ds2-5-body-xs">The International Journal of Biochemistry & Cell Biology, 2002</p><p class="ds-related-work--abstract ds2-5-body-sm">We recently showed that melatonin counteracted mitochondrial oxidative stress and increased the activity of the mitochondrial oxidative phosphorylation (OXPHOS) enzymes both in vivo and in vitro. To further clarify these effects, we studied here the activity of OXPHOS enzymes and the synthesis of ATP in rat liver and brain mitochondria in vitro. In sub-mitochondrial particles, melatonin increases the activity of the complexes I and IV dose-dependently, the effect being significant between 1 and 10 nM. Blue native-PAGE followed by histochemical analysis of the OXPHOS enzymes further showed the melatonin-induced increase of complex I activity. Titration studies show that melatonin counteracts the partial inhibition of complex IV induced by 5 M potassium cyanide. However, melatonin (up to 5 mM) was unable to recover the activity of complex IV when it was completely blocked by 100 M cyanide. These data suggest that the indoleamine could stimulate the activity of the non-inhibited part of the complex IV. Melatonin also increases the production of ATP in control mitochondria and counteracts the cyanide-induced inhibition of ATP synthesis. These results provide new hormonal mechanism regulating mitochondrial homeostasis and may explain, at least in part, the anti-aging and neuroprotective properties of melatonin.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Melatonin increases the activity of the oxidative phosphorylation enzymes and the production of ATP in rat brain and liver mitochondria","attachmentId":86809389,"attachmentType":"pdf","work_url":"https://www.academia.edu/80422170/Melatonin_increases_the_activity_of_the_oxidative_phosphorylation_enzymes_and_the_production_of_ATP_in_rat_brain_and_liver_mitochondria","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/80422170/Melatonin_increases_the_activity_of_the_oxidative_phosphorylation_enzymes_and_the_production_of_ATP_in_rat_brain_and_liver_mitochondria"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="5" data-entity-id="22442944" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/22442944/Protective_effects_of_exogenously_administered_or_endogenously_produced_melatonin_on_hyperbaric_oxygen_induced_oxidative_stress_in_the_rat_brain">Protective effects of exogenously administered or endogenously produced melatonin on hyperbaric oxygen-induced oxidative stress in the rat brain</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="43930929" href="https://independent.academia.edu/KadirDundar">Kadir Dundar</a><span>, </span><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="44049933" href="https://independent.academia.edu/TopalTurgut">Turgut Topal</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Clinical and Experimental Pharmacology and Physiology, 2005</p><p class="ds-related-work--abstract ds2-5-body-sm">1. Hyperbaric oxygen (HBO) is a widely used treatment modality in many diseases. A known side-effect of HBO is the production of reactive oxygen species (ROS). Many antioxidants, such as vitamins C and E, riboflavin and selenium, have been used successfully to scavenge the ROS produced by HBO administration.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Protective effects of exogenously administered or endogenously produced melatonin on hyperbaric oxygen-induced oxidative stress in the rat brain","attachmentId":43060833,"attachmentType":"pdf","work_url":"https://www.academia.edu/22442944/Protective_effects_of_exogenously_administered_or_endogenously_produced_melatonin_on_hyperbaric_oxygen_induced_oxidative_stress_in_the_rat_brain","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/22442944/Protective_effects_of_exogenously_administered_or_endogenously_produced_melatonin_on_hyperbaric_oxygen_induced_oxidative_stress_in_the_rat_brain"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="6" data-entity-id="15301663" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/15301663/Melatonin_and_mitochondrial_function">Melatonin and mitochondrial function</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="34398486" href="https://ugr.academia.edu/Dar%C3%ADoAcu%C3%B1acastroviejo">Darío Acuña-castroviejo</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Life Sciences, 2004</p><p class="ds-related-work--abstract ds2-5-body-sm">Melatonin is a natural occurring compound with well-known antioxidant properties. In the last decade a new effect of melatonin on mitochondrial homeostasis has been discovered and, although the exact molecular mechanism for this effect remains unknown, it may explain, at least in part, the protective properties found for the indoleamine in degenerative conditions such as aging as well as Parkinson's disease, Alzheimer's disease, epilepsy, sepsis and other injuries such as ischemia-reperfusion. A common feature in these diseases is the existence of mitochondrial damage due to oxidative stress, which may lead to a decrease in the activities of mitochondrial complexes and ATP production, and, as a consequence, a further increase in free radical generation. A vicious cycle thus results under these conditions of oxidative stress with the final consequence being cell death by necrosis or apoptosis. Melatonin is able of directly scavenging a variety of toxic oxygen and nitrogen-based reactants, stimulates antioxidative enzymes, increases the efficiency of the electron transport chain thereby limiting electron leakage and free radical generation, and promotes ATP synthesis. Via these actions, melatonin preserves the integrity of the mitochondria and helps to maintain cell functions and survival. D . Synergistic effects of melatonin and deprenyl against MPTP-induced mitochondrial damage and DA depletion. Neurobiology of Aging 24 (3), 491 -500. Kilanczyk, E., Bryszewska, M., 2003. The effect of melatonin on antioxidant enzymes in human diabetic skin fibroblasts. . Modification of nitric oxide synthase activity and neuronal response in rat striatum by melatonin and kynurenine derivatives. . Structure-related inhibition of calmodulin-dependent neuronal nitric-oxide synthase activity by melatonin and synthetic kynurenines. Molecular Pharmacology 58 , 967 -975. Leist, M., Volbracht, C., Fava, E., Nicotera, P., 1998. 1-Methyl-4-phenylpyridinium induces autocrine excitotoxicity, protease activation, and neuronal apoptosis. Molecular Pharmacology 54 (5), 789 -801.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Melatonin and mitochondrial function","attachmentId":43351392,"attachmentType":"pdf","work_url":"https://www.academia.edu/15301663/Melatonin_and_mitochondrial_function","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/15301663/Melatonin_and_mitochondrial_function"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="7" data-entity-id="13441881" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/13441881/Some_biochemical_properties_of_melatonin_and_the_characterization_of_a_relevant_metabolite_arising_from_its_interaction_with_H2O2">Some biochemical properties of melatonin and the characterization of a relevant metabolite arising from its interaction with H2O2</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="32664637" href="https://unipd.academia.edu/GiuseppeZagotto">Giuseppe Zagotto</a><span>, </span><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="32724973" href="https://independent.academia.edu/DanieleDalzoppo">Daniele Dalzoppo</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Journal of Pineal Research, 2003</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Some biochemical properties of melatonin and the characterization of a relevant metabolite arising from its interaction with H2O2","attachmentId":45338958,"attachmentType":"pdf","work_url":"https://www.academia.edu/13441881/Some_biochemical_properties_of_melatonin_and_the_characterization_of_a_relevant_metabolite_arising_from_its_interaction_with_H2O2","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/13441881/Some_biochemical_properties_of_melatonin_and_the_characterization_of_a_relevant_metabolite_arising_from_its_interaction_with_H2O2"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div></div></div><div class="ds-sticky-ctas--wrapper js-loswp-sticky-ctas hidden"><div class="ds-sticky-ctas--grid-container"><div class="ds-sticky-ctas--container"><button class="ds2-5-button js-swp-download-button" data-signup-modal="{"location":"continue-reading-button--sticky-ctas","attachmentId":96013921,"attachmentType":"pdf","workUrl":null}">See full PDF</button><button class="ds2-5-button ds2-5-button--secondary js-swp-download-button" data-signup-modal="{"location":"download-pdf-button--sticky-ctas","attachmentId":96013921,"attachmentType":"pdf","workUrl":null}"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span>Download PDF</button></div></div></div><div class="ds-below-fold--grid-container"><div class="ds-work--container js-loswp-embedded-document"><div class="attachment_preview" data-attachment="Attachment_96013921" style="display: none"><div class="js-scribd-document-container"><div class="scribd--document-loading js-scribd-document-loader" style="display: block;"><img alt="Loading..." src="//a.academia-assets.com/images/loaders/paper-load.gif" /><p>Loading Preview</p></div></div><div style="text-align: center;"><div class="scribd--no-preview-alert js-preview-unavailable"><p>Sorry, preview is currently unavailable. 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