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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.

drug metabolism and drug interactions

PREVENTIVE EFFECT OF ISOFLURANE ON DESTRUCTION OF CYTOCHROME P450 DURING REDUCTIVE DEHALOGENATION OF CARBON TETRACHLORIDE IN GUINEA-PIG LIVER MICROSOMES