Effect of hypoxia on carbon tetrachloride hepatotoxicity.
The effect of hypoxia on carbon tetrachloride-induced hepatotoxicity was studied. Male rats were exposed to carbon tetrachloride for 2 hr in the presence of differing oxygen concentrations. Serum glutamate-pyruvate transaminase (SGPT) activities were measured 24 hr after the end of the exposure. Exposure of rats to 5000 ppm carbon tetrachloride in the presence of 100, 21, 12, or 6% oxygen resulted in SGPT activities of 489, 420, 3768, and 1788 I.U./l respectively. Exposure of rats to air and 0, 1250, 2500, 5000, or 7500 ppm carbon tetrachloride gave SGPT activities of 35, 32, 69, 420, and 2188 I.U./l respectively; when 12% oxygen was used, the corresponding SGPT activities were 32, 665, 691, 3768, and 4200 I.U./l respectively. Exposure of rats to hypoxia produced histopathologically detectable condensation of hepatic cytoplasmic material, and exposure to 5000 ppm carbon tetrachloride in the presence of air produced mild centrilobular necrosis, which was much more severe when rats were exposed to 5000 pm carbon tetrachloride in the presence of 12% oxygen. Hepatic microsomal conjugated diene concentrations were increased by hypoxia and by exposure to carbon tetrachloride, but no synergistic interaction was observed. Hepatic microsomal cytochrome P-450 concentrations were decreased after exposure to carbon tetrachloride, but were the same after exposure to carbon tetrachloride and 12 or 21% oxygen. Hepatic carbon tetrachloride concentrations were the same in rats exposed to carbon tetrachloride in the presence of 12 or 21% oxygen; hepatic chloroform concentrations were higher in rats exposed to carbon tetrachloride in the presence of air than in the presence of 12% oxygen. The covalent binding of [14C]carbon tetrachloride metabolites to hepatic microsomal lipids and proteins was increased markedly by hypoxia as compared with normoxia. The covalent binding of metabolites of carbon tetrachloride to cellular macromolecules may play a role in the potentiation of carbon tetrachloride toxicity by hypoxia.
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D002252:Carbon Tetrachloride Poisoning / Q000503:physiopathology*; D056486:Chemical and Drug Induced Liver Injury / Q000503:physiopathology*; D002725:Chloroform / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D000860:Hypoxia / Q000503:physiopathology*; D008054:Lipid Peroxides / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats
D008054:Lipid Peroxides; D002725:Chloroform; D003577:Cytochrome P-450 Enzyme System; D000410:Alanine Transaminase