Pathogenesis of Carbon Tetrachloride-Induced Hepatocyte Injury Bioactivation of CCl4by Cytochrome P450 and Effects on Lipid Homeostasis

Autor: Boll, Meinrad, Weber, Lutz W. D., Becker, Eberhard, Stampfl, Andreas
Zdroj: Zeitschrift für Naturforschung C; February 2001, Vol. 56 Issue: 1-2 p111-121, 11p
Abstrakt: The CCl4-induced development of liver damage was studied in monolayer cultures of pri­mary rat hepatocytes: (1) CCl4caused accumulation of triglycerides in hepatocytes following cytochrome P450 induction with ß-naphthoflavone or metyrapone. Ethanol or a high dose of insulin plus triio­dothyronine had the same effect. (2) CCl4increased the synthesis of fatty acids and triglycer­ ides and the rate of lipid esterification. Cholesterol and phospholipid synthesis from acetate was also increased. (3) CCl4reduced ß-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) CCl4exerted a pronounced inhibitory effect on the exocytosis of macromolecules (albumin), but did not affect secretion of bile acids from hepatocytes.
Databáze: Supplemental Index