School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, People's Republic of China.
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, Shanghai, China.
Arch Toxicol. 2021 Feb;95(2):759-765. doi: 10.1007/s00204-020-02947-4. Epub 2020 Nov 18.
Pyrrolizidine alkaloids (PAs) are naturally occurring hepatotoxins widely present in hundreds of plant species and also known to contaminate many foodstuffs, such as grain, honey, and tea. The formation of pyrrole-protein adducts via metabolic activation of PAs has been suggested as a primary trigger initiating hepatotoxicity. The present study for the first time tested the suitability of pyrrole-hemoglobin adducts as a novel and specific biomarker of PA exposure in humans. The level and elimination kinetics of pyrrole-hemoglobin adducts were systematically investigated in the blood samples of 43 PA-induced liver injury (PA-ILI) patients. The results revealed significantly higher concentrations (84.50 ± 78.38 nM) and longer persistence (~ 4 months) of pyrrole-hemoglobin adducts than that (concentration: 9.53 ± 10.72 nM; persistence: ~ 2 months) of pyrrole-plasma protein adducts, our previously developed PA exposure biomarker. Our findings confirmed that pyrrole-hemoglobin adducts with higher level and longer persistence should serve as a more applicable PA exposure biomarker for future clinical diagnosis of PA-ILI in drug/herb-induced liver injury patients.
吡咯里西啶生物碱（PAs）是广泛存在于数百种植物中的天然肝毒素，也已知会污染许多食物，如谷物、蜂蜜和茶。代谢激活 PAs 形成吡咯蛋白加合物被认为是引发肝毒性的主要触发因素。本研究首次测试了吡咯血红蛋白加合物作为一种新型、特异性的 PA 暴露生物标志物在人类中的适用性。在 43 例 PA 诱导的肝损伤（PA-ILI）患者的血液样本中，系统研究了吡咯血红蛋白加合物的水平和消除动力学。结果显示，吡咯血红蛋白加合物的浓度（84.50±78.38 nM）显著更高，持续时间更长（约 4 个月），而我们之前开发的 PA 暴露生物标志物吡咯血浆蛋白加合物的浓度（9.53±10.72 nM）和持续时间（约 2 个月）。我们的发现证实，具有更高水平和更长持续时间的吡咯血红蛋白加合物应该作为一种更适用的 PA 暴露生物标志物，用于未来药物/草药诱导的肝损伤患者中 PA-ILI 的临床诊断。
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