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(A) Proposed metabolic activation pathway of three pyrrolizidine alkaloids. Lasiocarpine, riddelliine, and senkirkine undergo metabolic activation to their reactive metabolites including DHP esters and DHP that react with cellular macromolecules, leading to cytotoxicity and genotoxicity. (B) Representative LC-MS/MS chromatograms showing DHP formation in CYP-expressing TK6 cells exposed to 1 μM of lasiocarpine for 24 h.
