Hanafy M S, Bogan J A
Biochem Pharmacol. 1982 May 1;31(9):1765-71. doi: 10.1016/0006-2952(82)90682-7.
The nature of the reactive metabolite of 3-methylindole is investigated using microsomal preparations prepared from the lungs of cattle. Nucleophilic thiol agents, glutathione, L-cysteine and N-acetyl-L-cysteine, protected microsomal proteins against alkylation by the reactive metabolite of 3-methylindole. The cytosol fraction from the lungs of cattle increased the protective effect of these thiol agents. Pretreatment of sheep with diethylmaleate, which depletes glutathione, increased the severity of the pneumotoxic effect of 3-methylindole, whereas pretreatment with L-cysteine decreased the severity of this effect. These findings are consistent with a hypothesis that an electrophilic reactive metabolite of 3-methylindole is responsible for its pneumotoxic effect and implies that glutathione and glutathione S-transferases are involved in the detoxification of this reactive metabolite. Nucleophilic thiol agents can be useful in the prevention of reactive metabolite induced-lung injury.
利用从牛肺制备的微粒体制剂研究了3-甲基吲哚反应性代谢物的性质。亲核硫醇试剂、谷胱甘肽、L-半胱氨酸和N-乙酰-L-半胱氨酸可保护微粒体蛋白免受3-甲基吲哚反应性代谢物的烷基化作用。牛肺的胞质溶胶部分增强了这些硫醇试剂的保护作用。用马来酸二乙酯预处理绵羊会耗尽谷胱甘肽，从而增加3-甲基吲哚肺毒性作用的严重程度，而用L-半胱氨酸预处理则会降低这种作用的严重程度。这些发现与一种假设一致，即3-甲基吲哚的亲电反应性代谢物是其肺毒性作用的原因，这意味着谷胱甘肽和谷胱甘肽S-转移酶参与了这种反应性代谢物的解毒过程。亲核硫醇试剂可用于预防反应性代谢物诱导的肺损伤。
