Isoflurane prevents cytochrome P450 loss while enhancing reductive dehalogenation of carbon tetrachloride in microsomes

• Published in: Japanese Journal of Pharmacology Vol. 76; no. suppl.1; p. 231
• Main Author: Fujii, Kohyu
• Format: Journal Article
• Language: English; Japanese
• Published: The Japanese Pharmacological Society 1998
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1016/S0021-5198(19)41033-0

Effects of isoflurane on the cytochrome P450(CYP) loss during the anaerobic dechlorination of carbon tetrachloride in the liver microsomes of guinea pig were examined. Under anaerobic condition, chloroform was produced from carbon tetrachloride through the microsomes in the presence of NADPH, and that production of chloroform was increased to 1.80 times by the addition of isoflurane. The concentration of microsomal CYP decreased to 71.6% after 7 minutes incubation with carbon tetrachloride and NADPH. In the presence of isoflurane in the same incubation system, this CYP decreasing was to be 84.7%. The essential components for the loss of CYP during the dechlorination of carbon tetrachioride were microsomes, NADPH and carbon tetrachioride. The addition of carbon monoxide reduced the CYP loss to negligible. These findings indicate that isoflurane interacts with CYP to prevent the CYP destruction during the anaerobic dechlorination of carbon tetrachloride in the guinea pig liver microsomes. These results also suggest that the destruction of CYP during anaerobic dechlorination of carbon tetrachloride in the microsomes was caused by direct attack of the trichloromethyl radical, rather than by carbon tetrachloride-induced lipid peroxidation.