Inhibitory Effect of Paraquat on Biotransformation of Halothane in Rabbit Liver Microsomes
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Microsomal fractions were prepared from the liver of rabbits to investigate the effects of paraquat (methyl viologen) on generation of metabolites of halothane under the optimal aerobic and anaerobic conditions. Halothane (CF3CHClBr) is known to undergo oxidative and reductive biotransformation in the hepatic mixed function oxidase system including cytochrome-P450 reductase and cytochrome P450. The results showed that paraquat inhibited generation of metabolites of halothane under these conditions. Generation of the aerobic metabolite, trifluoroacetic acid (CF3COOH), and anaerobic metabolites, 2-chloro-1, 1, 1-trifluoroethane (CF3CH2Cl) and 2-chloro-1, 1-difluoroethylene (CF2CHC1), were inhibited 50% by 4.96 mM and 35.3 mM paraquat, respectively. Possible mechanisms were speculated on to account for the inhibitory effects: one being the impaired formation of halothane-cytochrome P450 complex by addition of paraquat, and the other the diversion of electrons from cytochrome-P450 reductase to generate active paraquat radicals. It is concluded that paraquat inhibits NADPH-dependent biotransformation of halothane catalyzed in mixed function oxidase system.
This study was supported in part by a Grant-in-aid for Scientific Research from the Ministry of Education, Science and Culture of Japan.
Hiroshima Journal of Medical Sciences
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Hiroshima University Medical Press
Departmental Bulletin Paper
Departmental Bulletin Papers
Graduate School of Biomedical Science