Ebel R E, Barlow R L, McGrath E A
Fundam Appl Toxicol. 1987 Feb;8(2):207-16. doi: 10.1016/0272-0590(87)90119-9.
CHCl3 hepatotoxicity was studied in the male Mongolian gerbil and compared to that in the male Sprague-Dawley strain rat. Based on elevations in serum transaminase activities in response to CHCl3 exposure, control gerbils were more sensitive to CHCl3 than were gerbils treated with phenobarbital, chlordecone, mirex, or 3-methylcholanthrene. The increased sensitivity of the control relative to the induced gerbil was consistent with earlier observations of CCl4 hepatotoxicity (Ebel, R. E., and McGrath, E. A., 1984, Toxicol, Lett., 22, 205-210). Microsomal enzyme concentrations or activities were not decreased in the control or induced gerbils in response to CHCl3 exposures of up to 200 microliter/kg. At a dose of 500 microliter/kg, cytochrome P-450 and its reductase were decreased by about 25% in the chlordecone-induced gerbil. In contrast, chlordecone- and phenobarbital-induced rats were sensitive to CHCl3 as evidenced by marked elevations in serum transaminase activities, decreases in microsomal enzyme concentrations or activities, and a transient decrease in hepatic nonprotein sulfhydryl groups. Control rats were insensitive to CHCl3. Histopathological changes in the livers of these animals were consistent with alterations in the biochemical parameters measured. The relationship between sensitivity to the hepatotoxic effects of CHCl3 and CCl4 was different for the gerbil and rat.
研究了氯仿对雄性蒙古沙鼠的肝毒性,并与雄性斯普拉格-道利品系大鼠进行了比较。基于氯仿暴露后血清转氨酶活性的升高,对照沙鼠比用苯巴比妥、十氯酮、灭蚁灵或3-甲基胆蒽处理的沙鼠对氯仿更敏感。相对于诱导沙鼠,对照沙鼠敏感性的增加与早期四氯化碳肝毒性的观察结果一致(埃贝尔,R.E.,和麦格拉思,E.A.,1984年,《毒理学快报》,22卷,205 - 210页)。在高达200微升/千克的氯仿暴露下,对照或诱导沙鼠的微粒体酶浓度或活性并未降低。在500微升/千克的剂量下,十氯酮诱导的沙鼠中细胞色素P - 450及其还原酶降低了约25%。相比之下,十氯酮和苯巴比妥诱导的大鼠对氯仿敏感,血清转氨酶活性显著升高、微粒体酶浓度或活性降低以及肝脏非蛋白巯基短暂降低证明了这一点。对照大鼠对氯仿不敏感。这些动物肝脏的组织病理学变化与所测生化参数的改变一致。沙鼠和大鼠对氯仿肝毒性作用的敏感性与四氯化碳的关系不同。