Effect of carbon tetrachloride—alcohol-induced liver fibrosis on microsomal mixed-function oxidases and the cytosolic glutathione-conjugating system in rat liver

Abstract

1. Subchronic treatment of male and female rats with CCl₄ (0.2 ml/kg orally twice weekly) and drinking water containing 5% ethanol for four weeks led to a 20 to 40-fold increase in serum sorbitol dehydrogenase activity and to an augmentation of the liver triglyceride and hydroxyproline contents, indicating steatosis and fibrosis, respectively. Liver fibrosis was less pronounced in females than in male rats.

2. As a consequence of these alterations the hepatic microsomal mixed-function oxidase activity as measured by aminopyrine demethylation was decreased with concomitant loss of cytochrome P-450 in both sexes. Aniline hydroxylation as well as the activity of the NADPH-cytochrome c reductase showed no significant alterations.

3. While the hepatic glutathione content remained unchanged, the cytosolic glutathione S-transferase activities towards both an aryl and an epoxide substrate were markedly decreased following the development of liver fibrosis both in male and female rats.