Garle M J, Fry J R
Department of Physiology and Pharmacology, Medical School, Queen's Medical Centre, Nottingham, U.K.
Toxicology. 1989 Jan;54(1):101-10. doi: 10.1016/0300-483x(89)90082-6.
The ability of 27 compounds to mediate depletion of glutathione (GSH) in a fortified liver microsome incubation via production of reactive metabolites generated by microsomal mono-oxygenase (MMO) metabolism has been studied. The majority of compounds tested of this type were positive in this assay, with the exception of iproniazid and naphthalene. Thioacetamide, the reactive metabolite of which binds via lysine residues, was negative. Acrolein and hexachlorobutadiene produced depletion in the absence of prior activation, as did menadione but for which enzyme induction increased the magnitude of depletion. Allyl alcohol produced MMO-mediated depletion of GSH. Some depletion of GSH occurred in the presence of common substrates of the MMO system. It is suggested that this depletion assay may be a valid test for detection of reactive metabolites generated by MMO metabolism.
研究了27种化合物通过微粒体单加氧酶（MMO）代谢产生的反应性代谢物，在强化肝微粒体孵育中介导谷胱甘肽（GSH）耗竭的能力。这类测试的大多数化合物在该试验中呈阳性，但异烟肼和萘除外。硫代乙酰胺的反应性代谢物通过赖氨酸残基结合，呈阴性。丙烯醛和六氯丁二烯在没有预先激活的情况下导致GSH耗竭，甲萘醌也是如此，但酶诱导增加了耗竭的程度。烯丙醇产生MMO介导的GSH耗竭。在MMO系统的常见底物存在下，GSH出现了一些耗竭。有人认为，这种耗竭试验可能是检测MMO代谢产生的反应性代谢物的有效测试。
