Modification of methanol potentiation of CCl4 toxicity in rats by chloramphenicol and salicylate.
The mechanisms by which methanol potentiates CCl4 hepatotoxicity was studied in rats. Chloramphenicol, an inhibitor of cytochrome P-450, blocked the increase of serum glutamate-oxaloacetate transaminase activity enhanced by methanol pretreatment of rats exposed to CCl4. Chloramphenicol also decreased microsomal lipid peroxidation in both CCl4 and methanol-pretreated, CCl4-intoxicated animals when measured 30 minutes after exposure. Chloramphenicol prevented the loss of glucose 6-phosphatase activity after CCl4 and methanol. Sodium salicylate, which lowers the level of NADPH in the hepatocyte, blocked methanol potentiation of CCl4 damage as measured by the elevation of serum GOT activity. Therefore, methanol may potentiate CCl4 hepatotoxicity by stimulation of CCl4 bioactivation by cytochrome P-450 via an increase in the level of reduced NAD(P)H in the liver.
D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002252:Carbon Tetrachloride Poisoning / Q000378:metabolism / Q000517:prevention & control*; D002701:Chloramphenicol / Q000494:pharmacology*; D004357:Drug Synergism; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D000432:Methanol / Q000037:antagonists & inhibitors / Q000633:toxicity*; D008862:Microsomes, Liver / Q000201:enzymology; D008930:Mitochondria, Liver / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012980:Sodium Salicylate / Q000494:pharmacology*
D008054:Lipid Peroxides; D002701:Chloramphenicol; D001219:Aspartate Aminotransferases; D012980:Sodium Salicylate; D000432:Methanol