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Pyrrole-protein adducts – A biomarker of pyrrolizidine alkaloid-induced hepatotoxicity
Journal of Food and Drug Analysis ( IF 3.6 ) Pub Date : 2018-07-01 , DOI: 10.1016/j.jfda.2018.05.005
Jiang Ma 1, 2 , Qingsu Xia 3 , Peter P Fu 3 , Ge Lin 1, 2
Affiliation  

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. The metabolic activation of PAs is catalyzed by hepatic cytochrome P450 and generates reactive pyrrolic metabolites that bind to cellular proteins to form pyrrole-protein adducts leading to PA-induced hepatotoxicity. The mechanisms that pyrrole-protein adducts induce toxicities have not been fully characterized. Methods for qualitative and quantitative detection of pyrrole-protein adducts have been developed and applied for the clinical diagnosis of PA exposure and PA-induced liver injury. This mini-review addresses the mechanisms of PA-induced hepatotoxicity mediated by pyrrole-protein adducts, the analytical methods for the detection of pyrrole-protein adducts, and the development of pyrrole-protein adducts as the mechanism-based biomarker of PA exposure and PA-induced hepatotoxicity.

中文翻译:

吡咯-蛋白质加合物——吡咯里西啶生物碱诱导的肝毒性的生物标志物

吡咯里西啶生物碱 (PA) 是在全球 6000 多种植物中发现的植物毒素。在大约 3% 的开花植物中发现了大约 600 种有毒 PA 和 PA N-氧化物。PA 可在不同器官中引起毒性,尤其是在肝脏中。PAs 的代谢活化由肝细胞色素 P450 催化并产生反应性吡咯代谢物,这些代谢物与细胞蛋白质结合形成吡咯-蛋白质加合物,导致 PA 诱导的肝毒性。吡咯-蛋白质加合物诱导毒性的机制尚未完全表征。吡咯-蛋白质加合物的定性和定量检测方法已被开发并应用于 PA 暴露和 PA 诱导的肝损伤的临床诊断。
更新日期:2018-07-01
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