Evidence for carbon tetrachloride-induced lipid peroxidation in mouse liver.
The involvement of lipid peroxidation in the mechanism of carbon tetrachloride-induced hepatotoxicity has been a point of controversy. Previous investigators have reported an absence of lipid peroxidative degradation products in mice after exposure to carbon tetrachloride and have used this evidence against the hypothesis that lipid peroxidation is an integral part of the events that cause tissue damage. We have compared the extent of lipid peroxidation caused by carbon tetrachloride between Sprague-Dawley rats and three strains of mice (A/J, BALB/cJ, and C57B1/6J) in in vitro and in vivo systems. Hepatic microsomes isolated from fasted mice of each strain produced more malondialdehyde (a degradation product of lipid peroxidation) per mg microsomal protein than those isolated from fasted rats at times of incubation with CCl4. In vivo lipid peroxidation was estimated by the lipid conjugated diene content in hepatic microsomes from the rat and three strains of mice. Increased conjugated diene formation was observed in microsomal lipids of these animals after intraperitoneal injection of CCl4 (1 ml/kg as a 20% solution in corn oil) when compared to animals given only corn oil, but no differences were found in the amount of conjugated dienes between mice and rats. Our observations show that the CCl4-treated mouse undergoes hepatic lipid peroxidation at least as well as the rat, and indicate that lipid peroxidation cannot be excluded as a mechanism of carbon tetrachloride hepatotoxicity as has been claimed on the basis of its ineffectiveness in the mouse.
D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D066298:In Vitro Techniques; D008054:Lipid Peroxides / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity
D008054:Lipid Peroxides; D008315:Malondialdehyde; D003577:Cytochrome P-450 Enzyme System; D002251:Carbon Tetrachloride