Kubow S, Bray T M
Department of Nutritional Sciences, College of Biological Science, University of Guelph, Ont., Canada.
Can J Physiol Pharmacol. 1988 Jul;66(7):863-7. doi: 10.1139/y88-140.
The relative roles of tissue glutathione and vitamin E concentrations in the pneumotoxicity of 3-methylindole were studied. Thirty-two goats were divided into four groups and pretreated with (i) vitamin E + cysteine, (ii) vitamin E + diethylmaleate, (iii) cysteine, and (iv) diethylmaleate to vary tissue concentrations of glutathione and (or) vitamin E. Lung tissue concentrations of glutathione, vitamin E, and cytochrome P-450 were measured after pretreatments in four of eight animals in each group. Groups pretreated with cysteine had higher glutathione levels in the lung than those of diethylmaleate-pretreated goats. Goats receiving vitamin E had significantly higher concentrations of vitamin E than unsupplemented groups. After pretreatments the other four goats in each group were challenged with 3-methylindole (0.03 g/kg body weight) by intrajugular infusion. The severity of lung lesions was evaluated and scored by gross and microscopic examination at 72 h after infusion. 3-Methylindole-induced lung lesions were severe when tissue glutathione was reduced and were mild when tissue glutathione was induced. Enhancement of tissue vitamin E did not significantly affect 3-methylindole toxicity. These results indicate that the initial toxicological event is likely to be the result of binding of 3-methylindole free radical covalently to cellular protein rather than lipid peroxidation.
研究了组织谷胱甘肽和维生素E浓度在3-甲基吲哚肺毒性中的相对作用。将32只山羊分为四组，分别用（i）维生素E + 半胱氨酸、（ii）维生素E + 马来酸二乙酯、（iii）半胱氨酸和（iv）马来酸二乙酯进行预处理，以改变组织中谷胱甘肽和（或）维生素E的浓度。每组八只动物中的四只在预处理后测量肺组织中谷胱甘肽、维生素E和细胞色素P - 450的浓度。用半胱氨酸预处理的组肺中谷胱甘肽水平高于用马来酸二乙酯预处理的山羊组。接受维生素E的山羊体内维生素E浓度明显高于未补充组。预处理后，每组另外四只山羊通过颈静脉输注接受3-甲基吲哚（0.03 g/kg体重）的攻击。在输注后72小时通过大体和显微镜检查评估肺损伤的严重程度并进行评分。当组织谷胱甘肽减少时，3-甲基吲哚诱导的肺损伤严重；当组织谷胱甘肽增加时，损伤较轻。组织维生素E的增加对3-甲基吲哚毒性没有显著影响。这些结果表明，最初的毒理学事件可能是3-甲基吲哚自由基与细胞蛋白共价结合的结果，而不是脂质过氧化的结果。
