title: Blood Pyrrole-Protein Adducts--A Biomarker of Pyrrolizidine Alkaloid-Induced Liver Injury in Humans.
abstract: Pyrrolizidine alkaloids (PAs) induce liver injury (PA-ILI) and is very likely to contribute significantly to drug-induced liver injury (DILI). In this study we used a newly developed ultra-high performance liquid chromatography-triple quadrupole-mass spectrometry (UHPLC-MS)-based method to detect and quantitate blood pyrrole-protein adducts in DILI patients. Among the 46 suspected DILI patients, 15 were identified as PA-ILI by the identification of PA-containing herbs exposed. Blood pyrrole-protein adducts were detected in all PA-ILI patients (100%). These results confirm that PA-ILI is one of the major causes of DILI and that blood pyrrole-protein adducts quantitated by the newly developed UHPLC-MS method can serve as a specific biomarker of PA-ILI.
authors.affiliation: a School of Biomedical Sciences, Faculty of Medicine , The Chinese University of Hong Kong , Hong Kong SAR , Hong Kong.
authors.forename: Jianqing
authors.initials: J
authors.lastname: Ruan
authors.affiliation: b Division of Gastroenterology, Zhongshan Hospital , Fudan University , Shanghai , P. R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Gao
authors.affiliation: a School of Biomedical Sciences, Faculty of Medicine , The Chinese University of Hong Kong , Hong Kong SAR , Hong Kong.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: a School of Biomedical Sciences, Faculty of Medicine , The Chinese University of Hong Kong , Hong Kong SAR , Hong Kong.|c Joint Research Laboratory for Promoting Globalization of Traditional Chinese Medicines between Shanghai Institute of Materia Medica , Chinese Academy of Sciences and The Chinese University of Hong Kong , Hong Kong SAR , Hong Kong.
authors.forename: Junyi
authors.initials: J
authors.lastname: Xue
authors.affiliation: b Division of Gastroenterology, Zhongshan Hospital , Fudan University , Shanghai , P. R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: c Joint Research Laboratory for Promoting Globalization of Traditional Chinese Medicines between Shanghai Institute of Materia Medica , Chinese Academy of Sciences and The Chinese University of Hong Kong , Hong Kong SAR , Hong Kong.|d State Key Laboratory of Drug Research & Natural Products Chemistry Department, Shanghai Institute of Materia Medica , Chinese Academy of Sciences , P. R. China.
authors.forename: Changqiang
authors.initials: C
authors.lastname: Ke
authors.affiliation: c Joint Research Laboratory for Promoting Globalization of Traditional Chinese Medicines between Shanghai Institute of Materia Medica , Chinese Academy of Sciences and The Chinese University of Hong Kong , Hong Kong SAR , Hong Kong.|d State Key Laboratory of Drug Research & Natural Products Chemistry Department, Shanghai Institute of Materia Medica , Chinese Academy of Sciences , P. R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Ye
authors.affiliation: e National Center for Toxicological Research , Jefferson , Arkansas , USA.
authors.forename: Peter Pi-Cheng
authors.initials: PP
authors.lastname: Fu
authors.affiliation: f Center for Developmental Therapeutics, Seattle Children's Research Institute, Division of Gastroenterology, Department of Pediatrics , University of Washington , Washington , USA.|g Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education , Shenyang Pharmaceutical University , Shenyang , China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Zheng
authors.affiliation: b Division of Gastroenterology, Zhongshan Hospital , Fudan University , Shanghai , P. R. China.
authors.forename: Jiyao
authors.initials: J
authors.lastname: Wang
authors.affiliation: a School of Biomedical Sciences, Faculty of Medicine , The Chinese University of Hong Kong , Hong Kong SAR , Hong Kong.|c Joint Research Laboratory for Promoting Globalization of Traditional Chinese Medicines between Shanghai Institute of Materia Medica , Chinese Academy of Sciences and The Chinese University of Hong Kong , Hong Kong SAR , Hong Kong.
authors.forename: Ge
authors.initials: G
authors.lastname: Lin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000097:blood*; D056486:Chemical and Drug Induced Liver Injury / Q000175:diagnosis*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006504:Hepatic Veno-Occlusive Disease / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000097:blood* / Q000737:chemistry; D011763:Pyrrolizidine Alkaloids / Q000097:blood* / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D018675:Toxicity Tests; D014118:Toxins, Biological / Q000737:chemistry / Q000378:metabolism
chemical_list: D015415:Biomarkers; D011758:Pyrroles; D011763:Pyrrolizidine Alkaloids; D014118:Toxins, Biological
keywords: hepatic sinusoidal obstruction syndrome; hepatotoxicity; pyrrole-protein adducts; pyrrolizidine alkaloids