Isoflurane enhances dechlorination of carbon tetrachloride in guinea-pig liver microsomes

Effect of isoflurane on the dechlorination of carbon tetrachloride to chloroform was investigated in the guinea-pig liver microsomes. Under anaerobic conditions, chloroform is produced from carbon tetrachloride through the microsomes in the presence of NADPH, and such production of chloroform was increased by the addition of isoflurane. The K(m) for the production of chloroform from carbon tetrachloride was decreased to 86% by isoflurane compared with the control; however the maximum velocity of chloroform production was also decreased to 50%. The formation of the 445 nm band in the mixture of reduced cytochrome P-450 and carbon tetrachloride, and cytochrome P-450 reduction by NADPH were both accelerated by isoflurane, without alteration of NADPH-cytochrome c reductase activity. These results indicate that trichloromethyl radical, an intermediate product of carbon tetrachloride, easily combines to the haeme part of cytochrome P-450, whereas the protein part combines to isoflurane after being reduced by NADPH, which results in acceleration of carbon tetrachloride dechlorination under a lower concentration of carbon tetrachloride. These results may have implications for other drugs that are administered during isoflurane anaesthesia.