Potentiation of carbon tetrachloride hepatotoxicity in rats by pretreatment with polychlorinated biphenyls.
Pretreatment of male rats with Aroclor 1254 at a dose of 25 mg/kg i.p. for 6 days resulted in potentiation of the hepatotoxicity of inhaled carbon tetrachloride (CCl4) as evidenced by a decrease in liver glucose-6-phosphatase and elevations of serum glutamic oxalacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), isocitrate dehydrogenase, and sorbitol dehydrogenase. Aroclor 1254 alone did not demonstrate hepatotoxicity. Aroclor 1254 administration resulted in large increases in cytochrome c reductase, cytochrome P-450 (448) AND P-Nitroanisole demethylation. Subsequent exposure to CCl4 vapor resulted in over 70% decreases in the latter two parameters. The potentiation was dose-dependent with a dose of 5 mg/kg or higher being effective. Aroclor 1260 administration gave results similar to those of Aroclor 1254, but Aroclor 1221 enhanced CCl4 toxicity to a lesser extent.
D000410:Alanine Transaminase / Q000097:blood; D000429:Alcohol Oxidoreductases / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D002252:Carbon Tetrachloride Poisoning / Q000201:enzymology / Q000503:physiopathology*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003579:Cytochrome Reductases / Q000378:metabolism; D004357:Drug Synergism; D005952:Glucose-6-Phosphatase / Q000378:metabolism; D007521:Isocitrate Dehydrogenase / Q000097:blood; D008099:Liver / Q000187:drug effects; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D009575:Nitroanisole O-Demethylase / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D011078:Polychlorinated Biphenyls / Q000494:pharmacology*; D051381:Rats; D013012:Sorbitol; D013329:Structure-Activity Relationship
D013012:Sorbitol; D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls; D009575:Nitroanisole O-Demethylase; D000429:Alcohol Oxidoreductases; D007521:Isocitrate Dehydrogenase; D003579:Cytochrome Reductases; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005952:Glucose-6-Phosphatase