Stevens J L, Anders M W
Chem Biol Interact. 1981 Oct;37(1-2):207-17. doi: 10.1016/0009-2797(81)90178-2.
The effects of cysteine, diethyl maleate and phenobarbital treatments and 2H-substitution on the hepatotoxicity of chloroform were investigated. Time course studies of covalent binding and hepatoxicity in phenobarbital-treated rats showed that covalent binding of 14C-label from [14C]chloroform was maximal at 6 h after chloroform administration while hepatotoxicity reached a peak at 18 h. Cysteine treatment reduced both covalent binding and hepatotoxicity, while diethyl maleate and phenobarbital treatments increased both the hepatotoxicity of chloroform and the covalent binding of chloroform metabolites to hepatic proteins. A deuterium isotope effect was present on chloroform-induced hepatotoxicity in diethyl maleate-treated rats suggesting that the previously reported inhibition of haloform metabolism by diethyl maleate occurs at a step in the reaction mechanism after phosgene production. These data support the concept that phosgene is the toxic intermediate in chloroform metabolism.
研究了半胱氨酸、马来酸二乙酯和苯巴比妥处理以及2H取代对氯仿肝毒性的影响。对苯巴比妥处理的大鼠进行的共价结合和肝毒性的时间进程研究表明，[14C]氯仿中14C标记的共价结合在氯仿给药后6小时达到最大值，而肝毒性在18小时达到峰值。半胱氨酸处理降低了共价结合和肝毒性，而马来酸二乙酯和苯巴比妥处理则增加了氯仿的肝毒性以及氯仿代谢产物与肝蛋白的共价结合。在马来酸二乙酯处理的大鼠中，氘同位素效应存在于氯仿诱导的肝毒性上，这表明先前报道的马来酸二乙酯对卤仿代谢的抑制作用发生在光气产生后的反应机制步骤中。这些数据支持光气是氯仿代谢中的有毒中间体这一概念。
