Fujii K
Department of Anesthesiology and Critical Care Medicine, Hiroshima University School of Medicine, Japan.
Drug Metabol Drug Interact. 1997;14(2):99-107. doi: 10.1515/dmdi.1997.14.2.99.
Effects of isoflurane on cytochrome P450 loss during anaerobic dechlorination of carbon tetrachloride in guinea pig liver microsomes were examined. Under anaerobic conditions, chloroform was produced from carbon tetrachloride by the microsomes in the presence of NADPH, and production of chloroform was increased 1.80 times by the addition of isoflurane. The concentration of microsomal cytochrome P450 decreased to 71.6% after 7 minutes incubation with carbon tetrachloride and NADPH. With the addition of isoflurane in the same incubation system, the decrease in cytochrome P450 was to 84.9%. The essential components for the loss of cytochrome P450 during the dechlorination of carbon tetrachloride were microsomes, NADPH and carbon tetrachloride. Addition of carbon monoxide reduced the cytochrome P450 loss to negligible. These findings indicate that isoflurane interacts with cytochrome P450 to prevent the cytochrome P450 destruction during the anaerobic dechlorination of carbon tetrachloride in guinea-pig liver microsomes. These results also suggest that the destruction of cytochrome P450 during anaerobic dechlorination of carbon tetrachloride in microsomes was caused by direct attack by the trichloromethyl radical, rather than by carbon tetrachloride-induced lipid peroxidation.
研究了异氟烷对豚鼠肝微粒体中四氯化碳厌氧脱氯过程中细胞色素P450损失的影响。在厌氧条件下，微粒体在NADPH存在的情况下由四氯化碳生成氯仿，添加异氟烷后氯仿生成量增加了1.80倍。与四氯化碳和NADPH孵育7分钟后，微粒体细胞色素P450浓度降至71.6%。在相同孵育体系中添加异氟烷后，细胞色素P450的减少量为84.9%。四氯化碳脱氯过程中细胞色素P450损失的必需成分是微粒体、NADPH和四氯化碳。添加一氧化碳可将细胞色素P450的损失降至可忽略不计。这些发现表明，异氟烷与细胞色素P450相互作用，以防止豚鼠肝微粒体中四氯化碳厌氧脱氯过程中细胞色素P450的破坏。这些结果还表明，微粒体中四氯化碳厌氧脱氯过程中细胞色素P450的破坏是由三氯甲基自由基的直接攻击引起的，而不是由四氯化碳诱导的脂质过氧化引起的。
