Asian Journal
Of Traditional Medicines

Abstract: Pyrrolizidine alkaloids (PAs) are hepatotoxic to domestic livestock and carcinogenic to laboratory rodents. Previous in vitro metabolism studies have shown that (±) 6, 7-dihydro-7- hydroxyl-1-(hydroxymethy)-5H- pyrrolizine (DHP) and pyrrolizidine N-oxide are major metabolites of PAs. In this study, the metabolism of monocrotaline converted to its N-oxide in rat liver microsomes was investigated. The monocrotaline metabolite, monocrotaline N-oxide, was identified by MS² analysis. Based on an established HPLC quantification method, the metabolic kinetic parameters of the formation of monocrotaline N-oxide were calculated as K_m=566.9 μM and V_max=483.8±14.04 nmol·min^-1·mg^-1protein. Furthermore, the activities of cytochrome P-450 enzymes (CYP450) and flavin-containing monooxygenases (FMO) on the formation of monocrotaline N-oxide by in vitro metabolism were evaluated by well characterized chemical inhibitors, which provided evidence that CYP450 and FMO are the major enzymes responsible for N-oxide metabolite formation from monocrotaline.

Key words: pyrrolizidine alkaloid, monocrotaline, monocrotaline N-oxide, CYP 450, FMO