Biomarker development and risk assessment of P450-mediated metabolism of pyrrolizidine alkaloids induced livery injury
Refereed conference paper presented and published in conference proceedings


摘要Drug induced liver injury (DILI), which nowadays is well accepted to include drugs and natural toxins (such as herbal remedies and dietary supplements) induced liver injury, is a severe and potentially lethal clinical event. With the worldwide increasing use of alternative medicines for health care and disease treatment, their safety problems attract more public concerns. However, comparing with orthodox drugs, there are less awareness and investigation of adverse effects/toxicity induced by herbal preparations. Herbal medicines consist of multi-ingredients acting on multi-targets, which makes the investigation of their adverse effects/toxicity much more difficult and challenging. Unlike well-recognized DILI caused by drugs, herb-induced liver injury (HILI) often has less public awareness. In the recent decades, HILI has been reported as one of the major causes of DILI worldwide. More importantly, certain hepatotoxic herbs may not only directly cause hepatotoxicity, but also aggravate the liver damage in patients who are sub-healthy and/or have already developed liver diseases. The diagnosis of HILI is challenging due to the lack of characteristic clinical features and specific tests. This has subsequently hindered withdrawal of the offending toxins from the patients and providing suitable and specific treatment for the patients. Pyrrolizidine alkaloids (PAs) are one of the most significant phytotoxins due to their wide distribution in the nature. To date, over 660 PAs and their N-oxides have been identified in more than 6000 plant species. PA-induced liver injury (PA-ILI) is one of the major causes of HILI. Yearly numerous incidences of PA-ILI associated with the intake of PA-containing herbal products and/or PA-contaminated foodstuffs occur worldwide, because the specific diagnosis for PA-ILI and the universal quality control method for PA-containing/contaminated remedies and foodstuffs are unavailable.
In the present presentation, our translational research from the basic science of delineating P450-mediated metabolic activation-induced mechanism of PA-ILI and developing specific mechanism-based biomarker to the transformation of such biomarker for clinical diagnosis of PA-ILI and risk assessment of PA exposure will be illustrated. In addition, our recent novel findings on hepatotoxicity in 18 patients ingested with PA N-oxide-containing herbs, and the mechanism of PA N-oxide-induced hepatotoxicity, which involves the biotransformation of PA N-oxides to the corresponding PAs followed by the similar metabolic activation and interaction of the reactive metabolites with proteins to cause liver injury will also be addressed.
著者Jiang MA, Mengbi YANG, Jianqing RUAN, Ge LIN
會議名稱2nd Ling-Nan International Conference on Pharmaceutical Sciences 2017

上次更新時間 2018-30-11 於 11:06