CYP-mediated metabolic activation and pyrrole-protein adduct formation - The cause and biomarker of pyrrolizidine alkaloid N-oxide-induced herbal hepatotoxicity in human
Refereed conference paper presented and published in conference proceedings



摘要Pyrrolizidine alkaloids (PAs) are one of the most significant phytotoxins due to their wide distribution in more than 6000 plant species. PAs and their N-oxides are often present together in the plants. To date, over 660 PAs and PA N-oxides have been identified. PAs can cause acute toxicity in different organs, such as liver and lung, and many also induce chronic diseases like liver fibrosis and cancers. PA intoxication, in particular PA-induced liver injury (PA-ILI), associated with the intake of PA-producing herbal products and/or PA-contaminated foodstuffs has been known for a long time, while whether PA N-oxides can also induce liver injury (PAN-ILI) in human is largely unknown. Recently, we provided the first evidence of PAN-ILI in 18 patients who ingested PA N-oxide-producing herbs and also investigated the initial biochemical mechanism of PAN-ILI. In this presentation, the mechanism of PAN-ILI via biotransformation of PA N-oxides to the corresponding PAs followed by the CYP-mediated metabolic activation, which generates reactive metabolites interacting with cellular proteins to form pyrrole-protein adducts leading to liver injury, will be illustrated and also compared with the similar mechanism of PA-ILI. In addition, the development of a specific mechanism-based biomarker, blood pyrrole-protein adducts, and the application of such biomarker for the clinical diagnosis of PA-ILI and PAN-ILI will be addressed.
著者Ge LIN
會議名稱6th Asia Pacific ISSX Meeting

上次更新時間 2018-30-11 於 10:00