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Oxidative/Nitrative Mechanism of Molsidomine Mitotoxicity Assayed by the Cytochrome c Reaction with SIN-1 in Models of Biological Membranes.
Paes de Barros, Marcelo; Casares Araujo-Chaves, Juliana; Marlise Mendes Brito, Adrianne; Lourenço Nantes-Cardoso, Iseli.
Afiliação
  • Paes de Barros M; Interdisciplinary Program in Health Sciences, Institute of Physical Activity Sciences and Sports (ICAFE), Cruzeiro do Sul University, Rua Galvão Bueno 868, São Paulo, São Paulo 01506-000, Brazil.
  • Casares Araujo-Chaves J; Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, São Paulo 09210-580, Brazil.
  • Marlise Mendes Brito A; Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, São Paulo 09210-580, Brazil.
  • Lourenço Nantes-Cardoso I; Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, São Paulo 09210-580, Brazil.
Chem Res Toxicol ; 33(11): 2775-2784, 2020 11 16.
Article em En | MEDLINE | ID: mdl-32706246
Molsidomine is currently used as a vasodilator drug for the treatment of myocardial ischemic syndrome and congestive heart failure, although still presenting some mitochondrial-targeted side effects in many human cells. As a model of molsidomine mitotoxicity, the reaction of cytochrome c with phosphatidylserine (PS)- and cardiolipin (CL)-containing liposomes was investigated in oxidative/nitrosative conditions imposed by SIN-1 decomposition, which renders peroxynitrite (ONOO-) as a main reactive product. In these conditions, the production of thiobarbituric acid-reactive substance (TBARs) and LOOH was affected by the lipid composition and the oxidative/nitrative conditions used. The oxidative/nitrative conditions were the exposure of lipids to SIN-1 decomposition, native cytochrome c after previous exposure to SIN-1, concomitantly to SIN-1 and native cytochrome c, native cytochrome c, and cytochrome c modified by SIN-1 that presents a less-rhombic heme iron (L-R cytc). TBARs and LOOH production by lipids and cytochrome c exposed concomitantly to SIN-1 differed from that obtained using L-R cytc and featured similar effects of SIN-1 alone. This result suggests that lipids rather than cytochrome c are the main targets for oxidation and nitration during SIN-1 decomposition. PS- and CL-containing liposomes challenged by SIN-1 were analyzed by Fourier transform infrared spectroscopy that revealed oxidation, trans-isomerization, and nitration. These products are consistent with reaction routes involving lipids and NOx formed via peroxynitrite or direct reaction of NO• with molecular oxygen that attacks LOOH and leads to the formation of substances that are not reactive with thiobarbituric acid.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Molsidomina / Citocromos c / Membranas Mitocondriais / Modelos Biológicos Limite: Humans Idioma: En Revista: Chem Res Toxicol Assunto da revista: TOXICOLOGIA Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Molsidomina / Citocromos c / Membranas Mitocondriais / Modelos Biológicos Limite: Humans Idioma: En Revista: Chem Res Toxicol Assunto da revista: TOXICOLOGIA Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos