Melatonin protects the cytochrome P450 system through a novel antioxidant mechanism

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dc.contributor.authorEugenia Letelier, Maria
dc.contributor.authorJara Sandoval, Jose
dc.contributor.authorMolina Berrios, Alfredo
dc.contributor.authorFaundez, Mario
dc.contributor.authorAracena Parks, Paula
dc.contributor.authorAguilera, Felipe
dc.date.accessioned2024-01-10T13:50:25Z
dc.date.available2024-01-10T13:50:25Z
dc.date.issued2010
dc.description.abstractMelatonin, an endogenous hormone, is used as an antioxidant drug in doses quite higher than the endogenous circulating levels of this hormone. Hepatic endoplasmic reticulum contains the cytochrome P450 (CYP450) system, which catalyzes one biotransformation pathway of melatonin; this organelle is also one of the main sources of reactive oxygen species in cells. Therefore, we proposed that the antioxidant activity of this hormone may have a biological relevance in the organelle where it is biotransformed. To evaluate this postulate, we used Fe3+/ascorbate, an oxygen free radical generating system that leads to lipid peroxidation, loss of protein-thiol content, and activation of UDP-glucuronyltransferase in rat liver microsomes. We found that mM concentrations of melatonin prevented all these oxidative phenomena. We also found that Fe3+/ascorbate leads to structural alterations in the CYP450 monooxygenase, the enzyme that binds the substrate in the CYP450 system catalytic cycle, probably through direct oxidation of the protein, and also inhibited p-nitroanisole O-demethylation, a reaction catalyzed by the CYP450 system. Notably, melatonin prevented both phenomena at mu M concentrations. We provide evidence suggesting that melatonin may be oxidized by oxygen free radicals. Thus, we postulate that melatonin may be acting as an oxygen free radical scavenger, and Fe3+/ascorbate-modified melatonin would be directly protecting the CYP450 system through an additional specific mechanism. Pharmacological relevance of this phenomenon is discussed. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
dc.fechaingreso.objetodigital21-03-2024
dc.format.extent7 páginas
dc.fuente.origenWOS
dc.identifier.doi10.1016/j.cbi.2010.03.020
dc.identifier.eissn1872-7786
dc.identifier.issn0009-2797
dc.identifier.pubmedidMEDLINE:20302852
dc.identifier.urihttps://doi.org/10.1016/j.cbi.2010.03.020
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/79530
dc.identifier.wosidWOS:000278169700007
dc.information.autorucQuímica;Faúndez M;S/I;174901
dc.issue.numero3
dc.language.isoen
dc.nota.accesocontenido parcial
dc.pagina.final214
dc.pagina.inicio208
dc.publisherELSEVIER IRELAND LTD
dc.revistaCHEMICO-BIOLOGICAL INTERACTIONS
dc.rightsacceso restringido
dc.subjectAntioxidant
dc.subjectCytochrome P450
dc.subjectFe3+/ascorbate
dc.subjectMelatonin
dc.subjectRat liver microsomes
dc.subjectReactive oxygen species
dc.subjectMICROSOMAL UDP-GLUCURONOSYLTRANSFERASE
dc.subjectMONOXIDE-BINDING PIGMENT
dc.subjectREACTIVE OXYGEN
dc.subjectRAT-LIVER
dc.subjectPINEAL-GLAND
dc.subjectHEMOGLOBIN
dc.subjectINHIBITION
dc.subjectMETABOLISM
dc.subjectGENERATION
dc.subjectRADICALS
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleMelatonin protects the cytochrome P450 system through a novel antioxidant mechanism
dc.typeartículo
dc.volumen185
sipa.codpersvinculados174901
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
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