Species differences in the hepatic microsomal metabolism of the pyrrolizidine alkaloid senecionine.

1. The comparative metabolism of the pyrrolizidine alkaloid (PA) senecionine was studied in vitro in incubations of rat, guinea pig, cow, horse, and sheep hepatic microsomes. 2. Levels of the toxic pyrrolic metabolite 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP) were higher from guinea pig incubations (39.9 nmol/mg protein) than from other species (range 0.07 to 7.5 nmol/mg); results disagree with prior studies which used nonspecific techniques and suggest that the guinea pig's resistance to certain PAs may be due to resistance to pyrrole toxicity rather than low pyrrole formation. 3. Minor differences in senecionine N-oxidation and hydrolysis existed between the various species.