Effects of dietary methionine and ethanol on acetaminophen hepatotoxicity in mice.
The possible interactive relationship between nutritional compromise of acetaminophen detoxification and ethanol enhancement of acetaminophen hepatotoxicity was studied in mice by using a 2-X-2 factorial design. Ethanol was administered to adult male mice at 0 or 15% solution in the drinking water, and dietary methionine levels were at 54 or 100% of the requirement. After 4 weeks, a significant reduction in the median lethal time (LT50) following a high dose of acetaminophen was seen in the methionine-deficient groups. Methionine deficiency also caused a reduction in hepatic glutathione levels in the control group and in mice receiving sublethal doses of acetaminophen. PGOT levels were increased significantly by methionine deficiency but were markedly increased by the interaction of ethanol treatment and methionine deficiency. Glutathione-S-transferase activity was not affected by any treatment combinations, and p-nitroanisole O-demethylase activity and relative liver weights were not increased because of chronic ethanol ingestion. These findings indicate that methionine deficiency causes glutathione reduction, which predisposes the mouse to increased acetaminophen hepatotoxicity. Ethanol consumption did not seem to potentiate the increased hepatotoxic effects caused by methionine deficiency, except as indicated by PGOT activity.
D000082:Acetaminophen / Q000633:toxicity*; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D004032:Diet; D000431:Ethanol / Q000633:toxicity*; D005978:Glutathione / Q000032:analysis; D005982:Glutathione Transferase / Q000032:analysis; D008099:Liver / Q000187:drug effects*; D008297:Male; D008715:Methionine / Q000172:deficiency / Q000378:metabolism*; D051379:Mice
D000082:Acetaminophen; D000431:Ethanol; D008715:Methionine; D005982:Glutathione Transferase; D001219:Aspartate Aminotransferases; D005978:Glutathione