Moslen M T, Reynolds E S, Boor P J, Bailey K, Szabo S
Res Commun Chem Pathol Pharmacol. 1977 Jan;16(1):109-20.
Liver microsomal enzyme activities and glutathione (GSH) contents of fasted male rats pretreated with phenobarbital (PBT) or vehicle controls were measured during and after exposure to trichloroethylene (TRI) (1% x 2 hr). TRI caused morphologic liver injury only in the pbt animals. Cytochrome P-450 and b5 contents were diminished by the end of the first hr of TRI exposure and NADH-cytochrome c reduction increased three-fold by eight hr in the PBT animals. The only change in vehicle animals exposed to TRI was a decrease in NADPH-cytochrome c reductase activity by eight hr. Hepatic GSH contents of vehicle animals, constant during TRI exposure, rose with time. In contrast, in PBT animals, hepatic GSH contents decreased during TRI exposure and then rebounded. Decreases in GSH were most profound in the microsomal fraction. When fed animals with approximately two-fold higher hepatic GSH levels than fasted animals were exposed to TRI, they had shorter anesthesia recovery times and less liver injury, although excreting similar or slightly more trichlorinated metabolite into their urine in 24 hr than their fasted counterparts. We suggest that the hepatoxic effects of trichloroethylene are caused by inadequate detoxification of its reactive intermediates.
在禁食雄性大鼠接触三氯乙烯（TRI）（1%×2小时）期间及之后，测量预先用苯巴比妥（PBT）处理或作为载体对照的大鼠的肝脏微粒体酶活性和谷胱甘肽（GSH）含量。TRI仅在PBT处理的动物中引起肝脏形态学损伤。在TRI暴露的第一个小时结束时，细胞色素P - 450和b5含量降低，并且在PBT处理的动物中，NADH - 细胞色素c还原在8小时内增加了三倍。暴露于TRI的载体对照动物中唯一的变化是在8小时时NADPH - 细胞色素c还原酶活性降低。载体对照动物的肝脏GSH含量在TRI暴露期间保持恒定，并随时间升高。相反，在PBT处理的动物中，肝脏GSH含量在TRI暴露期间下降，然后反弹。GSH的降低在微粒体部分最为显著。当肝脏GSH水平比禁食动物高约两倍的喂食动物暴露于TRI时，它们的麻醉恢复时间更短，肝脏损伤更小，尽管它们在24小时内尿液中排出的三氯代代谢物与禁食动物相似或略多。我们认为三氯乙烯的肝毒性作用是由其反应性中间体的解毒不足引起的。
