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

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.