Inhibition of Microsomal Monooxygenases by the Enzyme Inductor Flumecinol

Eva Kvasničková (kvasnice@faf.cuni.cz), Alice Riegrová, Ivo M. Hais

Department of Biochemical Sciences, Faculty of Pharmacy, Charles University, Hradec Králové

Summary

Flumecinol is a drug used as barbital-type inducer of enzymes which oxygenate and conjugate some xenobiotics. In the present study its inducing effect on pethidine O-demethylase and amidopyrin demethylase, not on aniline hydroxylase, has been demonstrated in rats. Flumecinol inhibits the former two enzymes, does not inhibit aniline hydroxylase. The inhibition of pethidine demethylase and amidopyrin demethylase has been shown to be competitive. The finding of Grossman (1985) oral communication that flumecinol decreases hepatotoxicity of aflatoxin AFB₁ has prompted this study, but our results do not suggest that their observation could be explaine by the inhibition of haemoprotein P-450-dependent enzymes which toxicate aflatoxins to their epoxides, since the moderate inhibition of some oxygenases observed here does not affect the “toxicating” enzymes. It can be speculated that hepatotoxicity of aflatoxin B₁ could have been reduced by induction of O-demethylating and conjugating enzymes.