Siegers C P, Frühling A, Younes M
Acta Pharmacol Toxicol (Copenh). 1983 Aug;53(2):125-9. doi: 10.1111/j.1600-0773.1983.tb01879.x.
In phenobarbital (phenemalum NFN)-pretreated male rats exposed to 1% halothane for 2 hrs under hypoxic conditions (10% O2), significant increases in serum enzyme activities of alanine aminotransferase and sorbitol dehydrogenase were observed 24 and 48 hrs later indicating liver damage. In this known model of halothane hepatotoxicity, pretreatment with (+)-catechin (200 mg/kg orally) or silybine (150 mg/kg orally) protected against halothane-induced liver injury, whereas diethyldithiocarbamate (200 mg/kg orally) failed to be effective. Halothane decreased the concentration of reduced glutathione in liver only under hypoxic conditions indicating that glutathione might be involved in the non-oxidative metabolic pathways of halothane. Free fluoride in plasma was used as a measure of non-oxidative defluorination of halothane. Higher plasma fluoride levels were observed under conditions which led to hepatotoxicity but did not correlate with the protective effects of the antidotes. This further supports the assumption that 2-chloro-1,1,1-trifluoroethane might be the radical intermediate responsible for halothane hepatotoxicity.
在苯巴比妥（苯巴比妥NFN）预处理的雄性大鼠中，在缺氧条件（10%氧气）下暴露于1%氟烷2小时，24和48小时后观察到丙氨酸转氨酶和山梨醇脱氢酶的血清酶活性显著增加，表明肝脏受损。在这个已知的氟烷肝毒性模型中，用（+）-儿茶素（口服200毫克/千克）或水飞蓟宾（口服150毫克/千克）预处理可预防氟烷诱导的肝损伤，而二乙基二硫代氨基甲酸盐（口服200毫克/千克）则无效。氟烷仅在缺氧条件下降低肝脏中还原型谷胱甘肽的浓度，表明谷胱甘肽可能参与氟烷的非氧化代谢途径。血浆中的游离氟化物用作氟烷非氧化脱氟的指标。在导致肝毒性的条件下观察到较高的血浆氟化物水平，但与解毒剂的保护作用无关。这进一步支持了2-氯-1,1,1-三氟乙烷可能是导致氟烷肝毒性的自由基中间体的假设。
