Reicks M M, Hathcock J N
Drug Nutr Interact. 1984;3(1):43-51.
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.
采用2×2析因设计，在小鼠中研究了对乙酰氨基酚解毒的营养缺乏与乙醇增强对乙酰氨基酚肝毒性之间可能的相互作用关系。给成年雄性小鼠饮用含0%或15%乙醇的溶液，并将膳食蛋氨酸水平设定为需求量的54%或100%。4周后，蛋氨酸缺乏组在给予高剂量对乙酰氨基酚后，半数致死时间（LT50）显著缩短。蛋氨酸缺乏还导致对照组和接受亚致死剂量对乙酰氨基酚的小鼠肝脏谷胱甘肽水平降低。蛋氨酸缺乏显著提高了谷丙转氨酶（PGOT）水平，但乙醇处理与蛋氨酸缺乏的相互作用使其显著升高。谷胱甘肽-S-转移酶活性不受任何处理组合的影响，慢性摄入乙醇也未导致对硝基苯甲醚O-脱甲基酶活性和相对肝脏重量增加。这些发现表明，蛋氨酸缺乏导致谷胱甘肽减少，使小鼠更容易受到对乙酰氨基酚肝毒性增加的影响。除PGOT活性所示外，乙醇摄入似乎并未增强蛋氨酸缺乏所致的肝毒性增加作用。
