Wang Y, Olson M J, Baker M T
Department of Anesthesia, University of Iowa, Iowa City 52242.
Biochem Pharmacol. 1993 Jul 6;46(1):87-94.
The abilities of halothane and the fluoroethane chlorofluorocarbon (CFC) substitutes, FC-123, FC-133a, FC-124, FC-134a and FC-125, to stimulate cytochrome P450 activities and 2-chloro-1,1-difluoroethene (CDE) defluorination in hepatic microsomes from phenobarbital-treated rabbits were compared. At 1% (v/v) each, halothane and FC-123 similarly increased the consumption of NADPH and O2 by 300 and 100%, respectively, over that in microsomes without substrate. FC-133a and FC-124 were less effective, increasing NADPH and O2 consumption by 150-200 and 70%. FC-134a and FC-125 were the least effective, increasing NADPH and O2 consumption by only 70 and 50%, respectively. No metabolism of any fluoroethane could be detected under the incubation conditions used. Halothane and FC-123 were most effective in stimulating CDE metabolism with increases of CDE defluorination ranging from 1.5- to 2-fold. FC-133a and FC-124 enhanced CDE oxidation 89 and 74%, respectively, and FC-134a and FC-125 had no effect. While CDE metabolism was enhanced in the presence of the fluoroethanes, no additional NADPH or O2 was consumed when halothane or FC-124 was incubated with CDE compared with incubations containing only halothane or FC-124. Log-log plots of NADPH consumption and CDE metabolism with the olive oil/gas partition coefficients of each fluoroethane showed linear relationships. These data demonstrate that the activity of the fluoroethanes in stimulating P450 activity and CDE metabolism is a function of their lipid solubility, and fluoroethane-enhanced CDE metabolism is related to the ability of these compounds to increase uncoupled P450 activity.
比较了氟烷和氟乙烷氯氟烃（CFC）替代物FC - 123、FC - 133a、FC - 124、FC - 134a和FC - 125刺激苯巴比妥处理的兔肝微粒体中细胞色素P450活性及2 - 氯 - 1,1 - 二氟乙烯（CDE）脱氟的能力。每种物质浓度均为1%（v/v）时，氟烷和FC - 123分别使NADPH和O₂的消耗量比无底物的微粒体增加300%和100%，增加幅度相似。FC - 133a和FC - 124效果较差，使NADPH和O₂消耗量分别增加150% - 200%和70%。FC - 134a和FC - 125效果最差，仅使NADPH和O₂消耗量分别增加70%和50%。在所使用的孵育条件下未检测到任何氟乙烷的代谢。氟烷和FC - 123在刺激CDE代谢方面最有效，CDE脱氟增加1.5至2倍。FC - 133a和FC - 124分别使CDE氧化增强89%和74%，而FC - 134a和FC - 125无作用。虽然在氟乙烷存在下CDE代谢增强，但与仅含氟烷或FC - 124的孵育相比，氟烷或FC - 124与CDE一起孵育时未消耗额外的NADPH或O₂。NADPH消耗量和CDE代谢与各氟乙烷的橄榄油/气体分配系数的对数 - 对数图呈线性关系。这些数据表明，氟乙烷刺激P450活性和CDE代谢的活性是其脂溶性的函数，且氟乙烷增强的CDE代谢与这些化合物增加未偶联P450活性的能力有关。
