Pyrrole-protein adducts e A biomarker of pyrrolizidine alkaloid-induced hepatotoxicity

Pyrrolizidine alkaloids (PAs) are phytotoxins identified in over 6000 plant species worldwide.Approximately 600 toxic PAs and PA N-oxides have been identified in about 3%flowering plants. PAs can cause toxicities in different organs particularly in the liver. Themetabolic activation of PAs is catalyzed by hepatic cytochrome P450 and generates reactivepyrrolic metabolites that bind to cellular proteins to form pyrrole-protein adducts leadingto PA-induced hepatotoxicity. The mechanisms that pyrrole-protein adducts induce toxicitieshave not been fully characterized. Methods for qualitative and quantitative detectionof pyrrole-protein adducts have been developed and applied for the clinical diagnosisof PA exposure and PA-induced liver injury. This mini-review addresses the mechanismsof PA-induced hepatotoxicity mediated by pyrrole-protein adducts, the analytical methodsfor the detection of pyrrole-protein adducts, and the development of pyrrole-protein adductsas the mechanism-based biomarker of PA exposure and PA-induced hepatotoxicity.