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dc.contributor.authorMingatto, Fábio Erminio-
dc.contributor.authorDorta, Daniel J.-
dc.contributor.authordos Santos, Aline B.-
dc.contributor.authorCarvalho, Ivone-
dc.contributor.authorda Silva, Carlos H. T. P.-
dc.contributor.authorda Silva, Vinicius B.-
dc.contributor.authorUyemura, Sergio A.-
dc.contributor.authordos Santos, Antonio C.-
dc.contributor.authorCurti, Carlos-
dc.date.accessioned2014-05-20T15:27:56Z-
dc.date.accessioned2016-10-25T18:02:55Z-
dc.date.available2014-05-20T15:27:56Z-
dc.date.available2016-10-25T18:02:55Z-
dc.date.issued2007-10-01-
dc.identifierhttp://dx.doi.org/10.1016/j.toxicon.2007.06.006-
dc.identifier.citationToxicon. Oxford: Pergamon-Elsevier B.V., v. 50, n. 5, p. 724-730, 2007.-
dc.identifier.issn0041-0101-
dc.identifier.urihttp://hdl.handle.net/11449/37856-
dc.identifier.urihttp://acervodigital.unesp.br/handle/11449/37856-
dc.description.abstractMonocrotaline is a pyrrolizidine alkaloid present in plants of the Crotalaria species, which causes cytotoxicity and genotoxicity, including hepatotoxicity in animals and humans. It is metabolized by cytochrome P-450 in the liver to the alkylating agent dehydromonocrotaline. We evaluated the effects of monocrotaline and its metabolite on respiration, membrane potential and ATP levels in isolated rat liver mitochondria, and on respiratory chain complex I NADH oxidase activity in submitochondrial particles. Dehydromonocrotaline, but not the parent compound, showed a concentration-dependent inhibition of glutamate/malate-supported state 3 respiration (respiratory chain complex 1), but did not affect succinate-supported respiration (complex II). Only dehydromonocrotaline dissipated mitochondrial membrane potential, depleted ATP, and inhibited complex I NADH oxidase activity (IC50 = 62.06 mu M) through a non-competitive type of inhibition (K-I = 8.1 mu M). Therefore, dehydromonocrotaline is an inhibitor of the activity of respiratory chain complex I NADH oxidase, an action potentially accounting for the well-documented monocrotaline's hepatotoxicity to animals and humans. The mechanism probably involves change of the complex I conformation resulting from modification of cysteine thiol groups by the metabolite. (c) 2007 Elsevier Ltd. All rights reserved.en
dc.format.extent724-730-
dc.language.isoeng-
dc.publisherElsevier B.V.-
dc.sourceWeb of Science-
dc.subjectmonocrotalinept
dc.subjectdehydromonocrotalinept
dc.subjectliver mitochondriapt
dc.subjectrespiratory chain complex 1pt
dc.subjectNADH oxidase activitypt
dc.titleDehydromonocrotaline inhibits mitochondrial complex 1. A potential mechanism accounting for hepatotoxicity of monocrotalineen
dc.typeoutro-
dc.contributor.institutionUniversidade Estadual Paulista (UNESP)-
dc.contributor.institutionUniversidade de São Paulo (USP)-
dc.description.affiliationUniv Estadual Paulista, Fac Zootecn, Lab Bioquim, BR-17900000 Dracena, SP, Brazil-
dc.description.affiliationUniv São Paulo, Fac Ciências Farmaceut, Dept Quim Fis, BR-14040903 Ribeirao Preto, Brazil-
dc.description.affiliationUniv São Paulo, Fac Ciências Farmaceut, Dept Ciências Farmaceut, BR-14040903 Ribeirao Preto, Brazil-
dc.description.affiliationUniv São Paulo, Fac Ciências Farmaceut, Dept Anal Clin, BR-14040903 Ribeirao Preto, Brazil-
dc.description.affiliationUnespUniv Estadual Paulista, Fac Zootecn, Lab Bioquim, BR-17900000 Dracena, SP, Brazil-
dc.identifier.doi10.1016/j.toxicon.2007.06.006-
dc.identifier.wosWOS:000250310300013-
dc.rights.accessRightsAcesso restrito-
dc.relation.ispartofToxicon-
Appears in Collections:Artigos, TCCs, Teses e Dissertações da Unesp

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