谷胱甘肽状态对山羊体内3-甲基吲哚共价结合及肺毒性的影响。

Effect of glutathione status on covalent binding and pneumotoxicity of 3-methylindole in goats.

作者信息

Nocerini M R, Carlson J R, Breeze R G

出版信息

Life Sci. 1983 Jan 31;32(5):449-58. doi: 10.1016/0024-3205(83)90137-6.

Abstract

A study was conducted to investigate the relationship between glutathione (GSH) status, in-vivo metabolite covalent binding and 3-methylindole (3MI)-induced lung injury in goats. Cysteine or diethylmaleate pretreatments were given to sustain or deplete GSH, respectively, prior to intravenous 14C-3MI administration. Cysteine pretreatment prolonged survival times, decreased (P less than .05) covalent lung injury. Diethylmaleate pretreatment shortened survival times, increased (P less than .05) covalent binding and enhanced lung injury. Covalent binding was higher (P less than .05) in lung compared to liver and kidney. 3-Methylindole alone depleted GSH in 4 hours to 36, 66, and 75% of controls in these tissues, respectively. The relationship between tissue GSH, covalent binding and toxicity supports the hypothesis that 3MI-induced pneumotoxicity results from the formation of activated intermediates and that GSH plays a role in detoxication of these 3MI metabolites.

摘要

进行了一项研究，以调查山羊体内谷胱甘肽（GSH）状态、体内代谢物共价结合与3-甲基吲哚（3MI）诱导的肺损伤之间的关系。在静脉注射14C-3MI之前，分别给予半胱氨酸或马来酸二乙酯预处理以维持或消耗GSH。半胱氨酸预处理延长了存活时间，减少了（P<0.05）肺共价损伤。马来酸二乙酯预处理缩短了存活时间，增加了（P<0.05）共价结合并加重了肺损伤。肺中的共价结合高于肝脏和肾脏（P<0.05）。单独的3-甲基吲哚在4小时内使这些组织中的GSH分别降至对照的36%、66%和75%。组织GSH、共价结合与毒性之间的关系支持了以下假设：3MI诱导的肺毒性是由活性中间体的形成引起的，并且GSH在这些3MI代谢物的解毒中起作用。