Abstract

In vivo pretreatment of rats with phenobarbital or β-naphthoflavone reduced the specific activity of microsomal pyrrolizidine alkaloid N-oxide formation. Heat pretreatment of microsomes under conditions intended to selectively inactivate the flavin-containing monooxygenase did not lower the rate of N-oxidation. Incubation in the presence of cytochrome P-450 inhibitors diminished the microsomal formation of N-oxide. The observations are consistent with the hypothesis that pyrrolizidine alkaloid N-oxidation results primarily from the action of a constitutive isozyme of cytochrome P-450.

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