Microsomal metabolism of pyrrolizidine alkaloids: N-oxidation of seneciphylline and senecionine.

In vivo pretreatment of rats with phenobarbital or beta-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