TY - JOUR
T1 - Clinical application of pyrrole–hemoglobin adducts as a biomarker of pyrrolizidine alkaloid exposure in humans
AU - Ma, Jiang
AU - Zhang, Wei
AU - He, Yisheng
AU - Zhu, Lin
AU - Zhang, Chunyuan
AU - Liu, Jia
AU - Ye, Yang
AU - Zhuge, Yuzheng
AU - Lin, Ge
N1 - Funding Information:
This research was supported by Research Grants Council of Hong Kong (GRF Grants: 14111816 and 14106318) and The Chinese University of Hong Kong (Direct Grant: 4054503).
Publisher Copyright:
© 2020, Springer-Verlag GmbH Germany, part of Springer Nature
PY - 2021/2
Y1 - 2021/2
N2 - 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.
AB - 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.
KW - Diagnostic biomarkers
KW - Liver injury
KW - Pyrrole–hemoglobin adducts
KW - Pyrrole–plasma protein adducts
KW - Pyrrolizidine alkaloids
UR - http://www.scopus.com/inward/record.url?scp=85096209788&partnerID=8YFLogxK
U2 - 10.1007/s00204-020-02947-4
DO - 10.1007/s00204-020-02947-4
M3 - Journal article
C2 - 33210216
AN - SCOPUS:85096209788
SN - 0340-5761
VL - 95
SP - 759
EP - 765
JO - Archives of Toxicology
JF - Archives of Toxicology
IS - 2
ER -