Differences in early acetaminophen hepatotoxicity between obese ob/ob and db/db mice

摘要: Clinical investigations suggest that hepatotoxicity after acetaminophen (APAP) overdose could be more severe in the context of obesity and nonalcoholic fatty liver disease. The pre-existence fat accumulation CYP2E1 induction major mechanisms accounting for such hepatic susceptibility. To explore this issue, experiments were performed obese diabetic ob/ob db/db mice. Preliminary male female wild-type, ob/ob, mice showed a selective increase activity However, triglycerides these animals significantly lower compared with Next, APAP (500 mg/kg) was administered mice, carried out 0.5, 2, 4, 8 h intoxication. Liver injury intoxication higher as assessed by plasma transaminases, histology, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay. In however, extent glutathione depletion, levels APAP-protein adducts, c-Jun N-terminal kinase activation, changes gene expression, mitochondrial DNA not greater other genotypes. Furthermore, genotype lactate β-hydroxybutyrate specifically altered, whereas APAP-glucuronide intermediary between wild-type Thus, early APAP-induced than despite less similar basal transaminases. Hepatic have an important pathogenic role when occurs related metabolic disorders.