Dersham G, McMartin D, Dunbar D, Kaminsky L
Toxicol Appl Pharmacol. 1983 Oct;71(1):93-100. doi: 10.1016/0041-008x(83)90048-0.
The lethal effects of the fluorinated ether anesthetics fluroxene (2,2,2-trifluoroethyl vinyl ether) and its ethyl (TFEE) and allyl analogues in male Wistar rats have previously been demonstrated to be potentiated by specific hepatic microsomal cytochromes P-450, and mediated by the common metabolite 2,2,2-trifluoroethanol (TFE). We report here that administration of lethal combinations of anesthetic and cytochrome P-450-inducing agents or of lethal doses of TFE (0.21 g/kg and higher) to rats caused decreased white blood cell counts, necrosis of sternum bone marrow cells and lymphocytes in the thymic cortex, and resulted in Escherichia coli contamination of the blood, lungs, liver, and kidneys of treated rats. Control animals in identical environments were free of bacterial contamination. Pretreatment of rats with the antibiotic tetracycline-HCl in the drinking water (0.6 g/liter) from 24 hr before anesthetic or TFE administration significantly diminished the mortality. With TFEE and beta-naphthoflavone induction, mortality was reduced from 85 to 30% by the antibiotic. However, the antibody plaque assay following immunization with sheep erythrocytes indicated that the primary humoral immune response to a thymus-dependent antigen was not impaired in treated rats. These results considered together indicate that metabolic formation of TFE from the anesthetic agents produced a decreased host resistance with subsequent increased susceptibility to bacterial infection. If not administered the antibiotic, the animals succumbed to the infection.
先前已证明，在雄性Wistar大鼠中，氟化醚麻醉剂氟烯（2,2,2-三氟乙基乙烯基醚）及其乙基类似物（TFEE）和烯丙基类似物的致死效应会被特定的肝微粒体细胞色素P-450增强，并由共同代谢物2,2,2-三氟乙醇（TFE）介导。我们在此报告，给大鼠施用麻醉剂与细胞色素P-450诱导剂的致死组合或致死剂量的TFE（0.21 g/kg及更高），会导致白细胞计数减少、胸骨骨髓细胞坏死以及胸腺皮质中的淋巴细胞坏死，并导致受试大鼠的血液、肺、肝和肾受到大肠杆菌污染。处于相同环境中的对照动物没有细菌污染。在施用麻醉剂或TFE前24小时，用饮用水中的抗生素盐酸四环素（0.6 g/升）对大鼠进行预处理，可显著降低死亡率。在用TFEE和β-萘黄酮诱导的情况下，抗生素使死亡率从85%降至30%。然而，用绵羊红细胞免疫后的抗体空斑试验表明，受试大鼠对胸腺依赖性抗原的初次体液免疫反应并未受损。综合这些结果表明，麻醉剂代谢形成TFE会导致宿主抵抗力下降，随后对细菌感染的易感性增加。如果不施用抗生素，动物会死于感染。
