THE ROLE OF COVALENT BINDING AND LIPID-PEROXIDATION IN THE HEPATOTOXIC EFFECT OF CARBON-TETRACHLORIDE

4-[N-Sodium-N-(5-ethyl-1,3,4--thiadiazol-2-yl)]-sulfanilamido-5-methoxy-1,2-benzoquinone, which selectively inhibits lipid peroxidation (LPO), was used to investigate the hepatotoxic action of carbon tetrachloride in vivo. It was established that inactivation of the rat liver microsomal oxidation system, which occurs in the first hours after administration of CCl4, is due not to LPO processes but to covalent binding of radical metabolites of CCl4 to the corresponding enzymes. It was shown that the decrease in the activity of cytoplasmic enzymes of the antioxidative system - superoxide dismutase and catalase - observed in later period (after 48 h) also does not depend on LPO but is rather a consequence of covalent binding of CCl4 metabolites. However, the radical metabolites of CCl4 act indirectly in this case, probably through the system of protein synthesis. An analysis of the results obtained suggested that polyunsaturated acyls of liver phospholipids can function as a key link in the intracellular mechanism protecting enzymes and other macromolecules from the action of free radicals.