Pyrrolizidine Alkaloid-Protein Adducts: Potential Non-invasive Biomarkers of Pyrrolizidine Alkaloid-Induced Liver Toxicity and Exposure

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• 作者：Qingsu Xia ; Yuewei Zhao ; Ge Lin ; Frederick A. Beland ; Lining Cai ; Peter P. Fu
• 刊名：Chemical Research in Toxicology
• 出版年：2016
• 出版时间：August 15, 2016
• 年：2016
• 卷：29
• 期：8
• 页码：1282-1292
• 全文大小：682K
• 年卷期：0
• ISSN：1520-5010

文摘

Pyrrolizidine alkaloids (PAs) are phytochemicals present in hundreds of plant species from different families widely distributed in many geographical regions around the world. PA-containing plants are probably the most common type of poisonous plants affecting livestock, wildlife, and humans. There have been many large-scale human poisonings caused by the consumption of food contaminated with toxic PAs. PAs require metabolic activation to generate pyrrolic metabolites to exert their toxicity. In this study, we developed a novel method to quantify pyrrole-protein adducts present in the blood. This method involves the use of AgNO₃ in acidic ethanol to cleave the thiol linkage of pyrrole-protein (DHP-protein) adducts, and the resulting 7,9-di-C₂H₅O–DHP is quantified by HPLC-ES-MS/MS multiple reaction monitoring analysis in the presence of a known quantity of isotopically labeled 7,9-di-C₂D₅O–DHP internal standard. Using this method, we determined that diester-type PAs administered to rats produced higher levels of DHP-protein adducts than other types of PAs. The results suggest that DHP-protein adducts can potentially serve as minimally invasive biomarkers of PA exposure.