Efeitos tóxicos do etanol e sua relação com o estresse oxidativo

• Ano de defesa: 2005
• Autor(a) principal: Pivetta, Lucinéia Albanio
• Orientador(a): Farina, Marcelo
• Banca de defesa: Soares, Félix Alexandre Antunes
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Santa Maria
• Programa de Pós-Graduação: Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica
• Departamento: Bioquímica
• País: BR
• Palavras-chave em Português: Bioquimica toxicologica; Intoxicacao; Etanol; Doencas hepaticas; Estresse oxidativo
• Área do conhecimento CNPq: CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA
• Link de acesso: http://repositorio.ufsm.br/handle/1/11078

Ethanol is one of the most ingested substances among the different societies. So, it becomes target of several studies that intent to elucidate its mechanisms of toxicity. This study was aimed to better understand the link between ethanol and oxidative stress. Taking into account that thiol depletion is observed in ethanol injuries, two antioxidant compounds, N-acetylcysteine and ebselen, were tested, alone or simultaneously, against the effects of the chronic ethanol consumption on the cellular sulfhydryl status. The activities of glutathione peroxidase and δ-aminolevulinate dehydratase were evaluated in mice liver. Male Swiss albino mice received, during 30 days, a single administration of ethanol (3 g/kg) by gavage. This treatment caused a significant reduction in the levels of liver nonprotein thiols (NPSH). Daily intraperitoneal injections of either Nacetylcysteine (300 mg/kg) or ebselen (5 mg/kg) were able to blunt NPSH to the control levels. However, the simultaneous administration of N-acetylcysteine and ebselen did not show additive protective effect in this parameter. This phenomenon was also observed for the activities of liver glutathione peroxidase and δ-aminolevulinate dehydratase. Their activities were inhibited by ethanol and blunted by the individual treatment with N-acetylcysteine or ebselen. Liver NPSH were positively correlated with glutathione peroxidase and δ-aminolevulinate dehydratase activities. These results demonstrated that either N-acetylcysteine or ebselen, alone, are able to restore the harmful effects of ethanol consumption on enzymes whose catalytic activities depend on their thiol (δ-ALA-D) and selenol (GSH-Px) groups. The in vitro effects of crescent concentrations of acetaldehyde in the activities of mice liver glutathione peroxidase and glutathione reductase, cellular sulfhydryl status, thiol peroxidase activity of ebselen and the interaction between ebselen and glutathione were evaluated to better comprehend the relationship between acetaldehyde and the nucleophilic groups of biomolecules. Glutathione peroxidase and glutathione reductase activities in mice liver supernatants were not changed after pre-incubation with acetaldehyde. Acetaldehyde, up to 300 μM, did not affect the thiol-peroxidase activity of ebselen. Total sulfhydryl status was significantly reduced after the incubation with acetaldehyde (300 μM) and this phenomenon was also observed for NPSH at acetaldehyde concentrations of 100 and 300 μM. Taking into account that acetaldehyde, under these same above-mentioned conditions, did not oxidize glutathione and dithioerythritol in the absence of hepatic supernatant, these results indicate that the acetaldehyde-dependent oxidation of glutathione seems to depend, at least in part, on liver constituents.