Two Mechanisms of Cc14-Induced Fatty Liver: Lipid Peroxidation Or Covalent Binding Studied in Cultured Rat Hepatocytes

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Abstract
With cultured hepatocytes it was studied whether CCl4-induced inhibition of secretion of VLDL and HDL from liver cells is a consequence of covalent binding of CC14 metabolites (i.e. CO,; CC1,00) to cell constituents or of membrane damage by lipid peroxidation. Comparing the kinetics of inhibition of lipoprotein secretion with that of CCl4-bioactivation it was found, that covalent binding of (HC)-CC14 occurred at early time points (5 min) after CC14 administration and inhibited the lipoprotein secretion. At 100μM CC14 it was depressed by 53% within 60min. Incubations of CC14-treated cells with increasing concentrations of vitamin E blocked lipid peroxidation, but lipoprotein secretion was still inhibited. Piperonyl butoxid, a radical scavenger, protected against CCl4-induced inhibition of lipoprotein section, lipid peroxidation and covalent binding. These results show that during the early phases of CC14 poisoning fat accumulation is the consequence of covalent binding of CC14 metabolities to cell structures.