Fraser J M, Silkworth J B, Kaminsky L S
Toxicol Appl Pharmacol. 1986 Jun 15;84(1):84-92. doi: 10.1016/0041-008x(86)90418-7.
2,2,2-Trifluoroethanol (TFE) is the toxic metabolite of the anesthetic agent fluroxene. TFE treatment (0.21 g/kg, ip) of male Wistar rats significantly reduced peripheral white blood cell count, bone marrow nucleated cellularity, and dry weight of the small intestine. These toxic effects of TFE were first observed at 8 to 16 hr after treatment, persisted for 96 hr, and were accompanied by severe diarrhea and edema of the small intestine. A non-lethal dose of TFE increased the sensitivity of rats to bacterial endotoxin lethality by approximately 1000-fold. Antibiotic and antiendotoxin pretreatment reduced the lethality of TFE from 80 to 20% of the rats, but did not prevent the other toxic effects of TFE. In vitro experiments with serum from TFE-pretreated rats (0.13 g/kg) supported the growth of an average of 65% fewer cultured bone marrow cell colonies compared to the number of colonies produced when serum from control rats was used. This suggests that TFE-induced bone marrow depression and leukopenia are related to a decrease in colony stimulating factor activity. Taken together these results explain the rapid development of lethal bacterial infections in TFE-treated rats. TFE-mediated damage to the small intestine combined with prolonged leukopenia decreases the resistance of the rat to endogenous pathogens leading to systemic bacterial infection. In addition, the increased sensitivity to endotoxin induced by TFE leads to lethal endotoxemia.
2,2,2-三氟乙醇（TFE）是麻醉剂氟烯的有毒代谢产物。对雄性Wistar大鼠腹腔注射TFE（0.21 g/kg）可显著降低外周白细胞计数、骨髓有核细胞数以及小肠干重。TFE的这些毒性作用在治疗后8至16小时首次出现，持续96小时，并伴有严重腹泻和小肠水肿。非致死剂量的TFE使大鼠对细菌内毒素致死性的敏感性提高了约1000倍。抗生素和抗内毒素预处理将TFE的致死率从80%降低至20%，但并未阻止TFE的其他毒性作用。与使用对照大鼠血清时产生的集落数相比，用TFE预处理大鼠（0.13 g/kg）的血清进行体外实验显示，培养的骨髓细胞集落平均减少65%。这表明TFE诱导的骨髓抑制和白细胞减少与集落刺激因子活性降低有关。综合这些结果解释了TFE处理的大鼠中致命性细菌感染的快速发展。TFE介导的小肠损伤与长期白细胞减少相结合，降低了大鼠对内源性病原体的抵抗力，导致全身性细菌感染。此外，TFE诱导的对内毒素敏感性增加导致致命性内毒素血症。
