Plummer J L, Hall P D, Jenner M A, Cmielewski P L, Ilsley A H, Cousins M J
Department of Anaesthesia and Intensive Care, Flinders Medical Centre, Bedford Park, Australia.
Pharmacol Toxicol. 1988 Feb;62(2):74-9. doi: 10.1111/j.1600-0773.1988.tb01849.x.
Rats were exposed to halothane vapour, 50 p.p.m., or air for a period of four weeks. Within each exposure group, some animals drank plain water, some received water plus phenobarbitone, while some received water plus isoniazid. Halothane exposure resulted in increased serum bromide concentrations and liver injury evidenced by increased serum alanine aminotransferase activity, focal hepatocellular necrosis and fatty change. Administration of isoniazid reduced halothane metabolism by 33% as assessed by serum bromide concentrations, and completely blocked the injurious effects of halothane on the liver, suggesting that halothane metabolism plays a role in halothane hepatotoxicity under these conditions. Administration of phenobarbitone partially prevented the increase in serum alanine aminotransferase activity and hepatocellular necrosis due to halothane. In contrast to isoniazid, phenobarbitone led to a slight increase in halothane metabolism. However, phenobarbitone also caused an increase in liver size, such that the amount of halothane metabolised per gram of liver was reduced by phenobarbitone treatment. These results suggest that metabolism of halothane is an important factor in liver injury due to prolonged, subanaesthetic halothane exposure.
将大鼠暴露于50 ppm的氟烷蒸气或空气中四周。在每个暴露组中，一些动物饮用普通水，一些饮用加苯巴比妥的水，而一些饮用加异烟肼的水。氟烷暴露导致血清溴化物浓度升高以及肝脏损伤，表现为血清丙氨酸转氨酶活性增加、局灶性肝细胞坏死和脂肪变性。根据血清溴化物浓度评估，异烟肼的给药使氟烷代谢降低了33%，并完全阻断了氟烷对肝脏的损伤作用，这表明在这些条件下氟烷代谢在氟烷肝毒性中起作用。苯巴比妥的给药部分预防了因氟烷导致的血清丙氨酸转氨酶活性增加和肝细胞坏死。与异烟肼相反，苯巴比妥导致氟烷代谢略有增加。然而，苯巴比妥也导致肝脏大小增加，因此经苯巴比妥处理后每克肝脏代谢的氟烷量减少。这些结果表明，对于长时间亚麻醉剂量氟烷暴露导致的肝损伤，氟烷代谢是一个重要因素。
