Ascorbic acid protects against acetaminophen- and cocaine-induced hepatic damage in mice.
Administration of large doses of acetaminophen or cocaine to male CD-1 mice produces significant hepatic injury with marked elevation in serum glutamate-pyruvate transaminase activity and severe hepatocellular necrosis. The proposed mechanism for this phenomenon is activation of both parent compounds to hepatotoxic metabolites. Ascorbic acid, 1 g/kg, given to mice 1 hour before and 1 hour after either acetaminophen or cocaine treatment prevented development of the severe hepatocellular damage observed with administration of either drug alone. Plasma disappearance of acetaminophen was less rapid in ascorbic acid-treated animals, suggesting that in vivo metabolism of acetaminophen was altered by ascorbic acid treatment. However, ascorbic acid treatment alone produced a modest decrease in hepatic glutathione content and did not prevent marked hepatic glutathione depletion when administered concomitantly with acetaminophen. Furthermore, a 2-mM ascorbic acid concentration did not alter in vitro hepatic microsomal metabolism of cocaine as measured by formaldehyde formation. While the mechanism(s) for its protective effect remains to be elucidated, these results raise the possibility that ascorbic acid may be useful in preventing hepatic injury caused by some hepatotoxic drugs.
D000082:Acetaminophen / Q000378:metabolism / Q000633:toxicity*; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D003042:Cocaine / Q000378:metabolism / Q000633:toxicity*; D005978:Glutathione / Q000032:analysis; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains
D000082:Acetaminophen; D000410:Alanine Transaminase; D005978:Glutathione; D003042:Cocaine; D001205:Ascorbic Acid