Avaliação dos efeitos do tratamento crônico com neurolépticos e sua interação com substâncias potencialmente antioxidantes sobre parâmetros de estresse oxidativo no fígado e rim de ratos

• Ano de defesa: 2008
• Autor(a) principal: Dalla Corte, Cristiane Lenz
• Orientador(a): Soares, Félix Alexandre Antunes
• Banca de defesa: Burger, Marilise Escobar , Ferreira, Juliano
• 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: Flufenazina; Selênio; Disseleneto de difenila; Haloperidol; Valeriana officinalis; Interação planta medicinal-fármaco; Estresse oxidativo; TBARS; δ-ALA-D
• Palavras-chave em Inglês: Fluphenazine; Selenium; Diphenyl diselenide; Herb-drug interaction; Oxidative stress
• Área do conhecimento CNPq: CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA
• Link de acesso: http://repositorio.ufsm.br/handle/1/11086

Treatment with neuroleptic drugs has been associated to side effects like tardive diskynesia and hepatic damage. In spite of the several reports of hepatotoxicity after neuroleptic administration, few data are available in the literature about these effects and the precise mechanisms by which neuroleptics induce hepatotoxicity remain unclear. In the same way, there are few studies about the effects of neuroleptics on kidney. In this way, the first aim of the present work was to assess the effects of chronic exposure to fluphenazine in liver and kidney of rats, as well as the protective effect of diphenyl diselenide on the fluphenazine-induced damage (article 1). Long-term treatment with fluphenazine caused an increase in lipid peroxidation levels in liver and kidney homogenates, a decrease in hepatic SOD activity, and an increase in hepatic CAT activity. Diphenyl diselenide was able to protect liver and kidney from lipid peroxidation, ameliorate SOD activity in liver, and prevent the increase in hepatic CAT activity. Diphenyl diselenide treatment did not affect δ-ALA-D activity, but fluphenazine and/or in combination with diphenyl diselenide showed an inhibitory effect on δ-ALA-D activity in liver and kidney. The second objective of this study was to determine whether the treatment with haloperidol (HP), valerian or both in association impairs liver or kidney functions (article 2). Valerian did not affect oxidative stress parameters in the liver or kidney of rats. HP only increased glutathione (GSH) depletion in liver, but not in kidney. However, when HP was associated with valerian, an increase in lipid peroxidation levels and reactive species production was observed in the hepatic tissue. HP and valerian when administered independently did not affect the activity of hepatic and renal δ-ALA-D, however, these drugs administered concomitantly provoked an inhibition of hepatic δ-ALA-D activity. Serum aspartate aminotransferase (AST) activity was not altered by any treatment. However, serum alanine aminotransferase (ALT) activity was higher in the HP group and HP plus valerian group. Taken together, these results indicate the relationship between the treatment with flufenazine and the oxidative stress, and also point to the protective role of diphenyl diselenide on the oxidative damage induced by fluphenazine in liver. Our data also suggest adverse interactions between haloperidol and valerian treatments causing hepatic damage related to oxidative stress.