Pyrrole-protein adducts – A biomarker of pyrrolizidine alkaloid-induced hepatotoxicity |
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Authors: | Jiang Ma Qingsu Xia Peter P Fu Ge Lin |
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Institution: | 1. School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China;2. Joint Research Laboratory for Promoting Globalization of Traditional Chinese Medicines Between the Chinese University of Hong Kong and Shanghai Institute of Materia Medica, China Academy of Sciences, China;3. National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR, 72079, USA |
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Abstract: | 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. |
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Keywords: | Pyrrolizidine alkaloids Pyrrole-protein adducts Covalent binding Target protein Mechanism-based biomarker Clinical diagnosis |
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