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Genetically obese (ob/ob) mice are resistant to the lethal effects of thioacetamide hepatotoxicity.
Toxicol Appl Pharmacol ; 291: 38-45, 2016 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-26701066
ABSTRACT
Obesity increases the risk of chronic liver diseases, including viral hepatitis, alcohol-induced liver disease, and non-alcoholic steatohepatitis. In this study, we investigated the effects of obesity in acute hepatic failure using a murine model of thioacetamide (TA)-induced liver injury. Genetically obese ob/ob mice, together with non-obese ob/+ littermates, were subjected to a single intraperitoneal injection of TA, and examined for signs of hepatic injury. ob/ob mice showed a significantly higher survival rate, lower levels of serum alanine aminotransferase and aspartate aminotransferase, and less hepatic necrosis and apoptosis, compared with ob/+ mice. In addition, ob/ob mice exhibited significantly lower levels of malondialdehyde and significantly higher levels of glutathione and antioxidant enzyme activities compared with their ob/+ counterparts. Bioactivation analyses revealed reduced plasma clearance of TA and covalent binding of [(14)C]TA to liver macromolecules in ob/ob mice. Together, these data demonstrate that genetically obese mice are resistant to TA-induced acute liver injury through diminished bioactivation of TA and antioxidant effects.
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Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Assunto principal: Tioacetamida / Doença Hepática Induzida por Substâncias e Drogas / Obesidade Aspecto clínico: Etiologia Limite: Animais Idioma: Inglês Revista: Toxicol Appl Pharmacol Ano de publicação: 2016 Tipo de documento: Artigo País de afiliação: Coréia do Sul