Thioacetamide-induced hepatic damage in a rat nutritional model of steatohepatitis

Background: Nonalcoholic steatohepatitis is most often attributed to the effects of obesity, hyperlipidemia, diabetes mellitus and drugs. It is still unknown whether livers with steatohepatitis are more vulnerable to toxic damage. Aim: To determine the effect of the hepatotoxicant thioacetamide in a rat nutritional model of hepatic steatohepatitis. Methods: Steatohepatitis was induced in rats by placing them on a methionine-choline deficient diet for 1 month. Thioacetamide was administered by three consecutive intraperitoneal injections (300 mg/kg) at 24 h intervals. Results: Following treatment with thioacetamide, the elevated serum levels of liver enzymes and blood ammonia, liver necroinflammation and the survival rate after 48 h were not different between rats with normal or fatty liver. However, those parameters were significantly worse when steatohepatitis regressed after return to normal diet for 1 month (P < 0.01). Western blot analysis of hepatic extracts revealed no difference in cytochrome P4502E1 levels between livers with steatohepatitis and steatohepatitis after regression, suggesting that the enhanced hepatotoxicity after regression of steatohepatitis could not be attributed to increased cytochrome P4502E1. Conclusions: In a nutritional model of steatohepatitis, rats with fatty liver were not more vulnerable than normal rats to liver damage induced by thioacetamide. However, liver damage was significantly more severe in rats with steatohepatitis after 1 month regression. (C) 2004 Elsevier B.V. All rights reserved.