Pathogenesis of Carbon Tetrachloride-Induced Hepatocyte Injury Bioactivation of CCl4 by Cytochrome P450 and Effects on Lipid Homeostasis

Abstract

Abstract The CCl4-induced development of liver damage was studied in monolayer cultures of pri­mary rat hepatocytes: (1) CCl4 caused accumulation of triglycerides in hepatocytes following cytochrome P450 induction with β-naphthoflavone or metyrapone. Ethanol or a high dose of insulin plus triio­dothyronine had the same effect. (2) CCl4 increased the synthesis of fatty acids and triglycer­ ides and the rate of lipid esterification. Cholesterol and phospholipid synthesis from acetate was also increased. (3) CCl4 reduced β-oxidation of fatty acids as assessed by CO2-release and ketone body formation. Hydrolysis of triglycerides was also reduced. (4) The content of unsaturated fatty acids in microsomal lipids was decreased by almost 50% after incubation with CCl4, while saturated fatty acids increased slightly. (5) CCl4 exerted a pronounced inhibitory effect on the exocytosis of macromolecules (albumin), but did not affect secretion of bile acids from hepatocytes.