Pathogenesis of Carbon Tetrachloride-Induced Hepatocyte Injury Bioactivation of CC14 by Cytochrome P450 and Effects on Lipid Homeostasis

Abstract

(1) CC14 caused accumulation of triglycerides in hepatocytes following cytochrome P450 induction with β-naphthoflavone or metyrapone. Ethanol or a high dose of insulin plus triio-dothyronine had the same effect. (2) CC14 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) CC14 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) CC14 exerted a pronounced inhibitory effect on the exocytosis of macromolecules (albumin), but did not affect secretion of bile acids from hepatocytes. © 2001, Verlag der Zeitschrift für Naturforschung. All rights reserved.