Marsh J A, Ivanetich K M, Bradshaw J J, Harrison G G, Webber B L, Kaminsky L S
S Afr J Med Sci. 1975;40(4):205-17.
The role of the different cytochromes P-450 in the metabolism of the anaesthetic agent fluroxene, and the mechanism of production of toxic effects seen after pre-treatment of the animals with pehnobarbital prior to anaesthesia, have been investigated. Male rats were anaesthetized with fluroxene, or with 2,2,2-trifluroethyl ethyl ether, or with ethyl vinyl ether in an attempt to ascertain the in vivo toxic effects of the three anaesthetic agents. The resultant hepatic histology is reported. A study of the binding and metabolism of fluroxene by isolated rat hepatic microsomes was also made. We conclude that it is elevated levels of cytochrome P-450 which potentiate the toxicity of fluroxene anaesthesia in phenobarbital treated animals and that cytochrome P-448 does not bind or metabolize fluroxene. The potential toxicity of the fluroxene molecule is considered to reside in the trifluoroethyl moiety, while the vinyl group of fluroxene appears to play a role in the observed liver damage.
研究了不同细胞色素P - 450在麻醉剂氟烯代谢中的作用,以及在麻醉前用苯巴比妥预处理动物后出现毒性作用的机制。雄性大鼠分别用氟烯、2,2,2 - 三氟乙基乙醚或乙烯基乙醚麻醉,以确定这三种麻醉剂的体内毒性作用。报告了由此产生的肝脏组织学情况。还对分离的大鼠肝微粒体对氟烯的结合和代谢进行了研究。我们得出结论,在苯巴比妥处理的动物中,细胞色素P - 450水平升高会增强氟烯麻醉的毒性,并且细胞色素P - 448不与氟烯结合或代谢。氟烯分子的潜在毒性被认为存在于三氟乙基部分,而氟烯的乙烯基似乎在观察到的肝脏损伤中起作用。