Bray T M, Carlson J R, Nocerini M R
Proc Soc Exp Biol Med. 1984 May;176(1):48-53. doi: 10.3181/00379727-176-41841.
Covalent binding of 3-[14C]methylindole (3[14C]MI) in crude microsomal preparations of goat lung, liver, and kidney was measured to determine if a reactive intermediate was formed during the in vitro metabolism of 3-methylindole (3MI). The bound radioactivity was highest in lung compared to liver and kidney. The amount of bound radioactivity per nanomole of cytochrome P-450 was approximately 10 times higher in the lung compared to liver. No detectable bound radioactivity was found when 3-[3H]methyloxindole was used as the substrate. Cofactor requirements and the effects of inhibitors indicate that a mixed function oxidase (MFO) system is involved in formation of a reactive intermediate. Inhibitors and conjugating agents that are known to reduce the severity of 3MI-induced lung injury such as piperonyl butoxide (MFO inhibitor) and glutathione (conjugating agent) significantly decreased the in vitro binding of 3[14C]MI. The results indicate that a reactive intermediate is produced during the metabolism of 3MI by the MFO system. The organ specificity in binding suggests that covalent binding by lung microsomes may be related to the mechanism of 3MI-induced lung injury.
测定了3-[¹⁴C]甲基吲哚（3[¹⁴C]MI）在山羊肺、肝和肾的粗微粒体制剂中的共价结合，以确定在3-甲基吲哚（3MI）的体外代谢过程中是否形成了反应性中间体。与肝和肾相比，肺中的结合放射性最高。每纳摩尔细胞色素P-450的结合放射性量在肺中比在肝中高约10倍。当使用3-[³H]甲基氧化吲哚作为底物时，未发现可检测到的结合放射性。辅助因子需求和抑制剂的作用表明，混合功能氧化酶（MFO）系统参与了反应性中间体的形成。已知能降低3MI诱导的肺损伤严重程度的抑制剂和缀合剂，如胡椒基丁醚（MFO抑制剂）和谷胱甘肽（缀合剂），显著降低了3[¹⁴C]MI的体外结合。结果表明，MFO系统在3MI的代谢过程中产生了反应性中间体。结合的器官特异性表明，肺微粒体的共价结合可能与3MI诱导的肺损伤机制有关。
