Attenuation of carbon tetrachloride toxicity in acute hepatosteatosis induced by intake of a high carbohydrate diet after food deprivation (959.1)

Abstract

Hepatic fat accumulation constitutes a major component in the pathogenesis of liver injury. We determined the impact of lipid deposition in liver on cytochrome P‐450 (CYP) system and CCl4‐induced hepatotoxicity. Rats were fasted for 48 h, and then provided with a high‐carbohydrate/fat‐free diet (FH) or a normal diet (FN) for 48 h. Hepatic triglyceride level was not different between the normal control and the FN group, but 4 times greater in the FH group, which was consistent with the histopathological observation. FN intake resulted in a small increase in microsomal p‐nitrophenol hydroxylase, p‐nitroanisole O‐demethylase, and erythromycin N‐demethylase activities, but aminopyrine N‐demethylase was decreased. The microsomal enzyme activities determined were all inhibited markedly by FH intake. Immunoblotting analysis showed that proteins of CYP2E1, 1A, 3A, and 2B1/2 were decreased in the rats fed FH. Expression of CYP mRNAs was also down‐regulated. A dose of CCl4 was administered to the rats fed the different diets. The resulting liver injury was significantly lower in the FH group than in the FN group as determined by elevation of serum enzyme activities and histopathological examination. The results indicate that acute hepatosteatosis can precipitate erratic responses to various endogenous and exogenous substances via alterations in hepatic CYP‐mediated metabolizing capacity.