Pyrrole-protein adducts: metabolism-mediated mechanism-based biomarker and etiology of pyrrolizidine alkaloids intoxication
Refereed conference paper presented and published in conference proceedings



摘要Pyrrolizidine alkaloids (PAs) are significant phytotoxins widely distributed in plant species and cause hepatotoxicity due to human exposure to PA-producing natural products/PA-contaminated foodstuffs. PAs induce liver injury (PA-ILI) via CYPs-mediated metabolic activation to generate reactive metabolites, dehydro-PAs which bind with cellular proteins to form pyrrole-protein adducts (PPA), leading to hepatotoxicity. Our group identified that all dehydro-PAs contain an identical core structure regardless of different structures of PAs. This finding led the foundation for developing a novel mechanism-based biomarker for diagnosis of PA exposure. Our developed LC-MS/MS methodology to determine PPA provides a paradigm shift in diagnosis of PA-ILI and has been well received and recommended for testing PA-ILI patients in China and in Ethiopia. In this presentation, our study of PA-ILI from the identification of clinical problems, to the laboratory basic science for delineating toxic mechanism and developing biomarker, and then the transformation of biomarker determination for clinical diagnosis will be illustrated. [The study was supported by GRF Grants (Ref Nos.: 14160817 and 14106318), and CUHK Project Impact Enhancement Fund (PIEF 3133029) and Direct Grant (Ref Nos.: 4054503)]
著者LIN Ge
會議名稱The 3rd Ling-nan International Conference of Pharmaceutical Sciences and The 4th Ling-nan International DMPK Forum

上次更新時間 2020-26-11 於 12:30