title: Pyrrolizidine Alkaloid-Protein Adducts: Potential Non-invasive Biomarkers of Pyrrolizidine Alkaloid-Induced Liver Toxicity and Exposure.
abstract: 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.
authors.affiliation: National Center for Toxicological Research , Jefferson, Arkansas 72079, United States.
authors.forename: Qingsu
authors.initials: Q
authors.lastname: Xia
authors.affiliation: National Center for Toxicological Research , Jefferson, Arkansas 72079, United States.
authors.forename: Yuewei
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong , Hong Kong SAR.
authors.forename: Ge
authors.initials: G
authors.lastname: Lin
authors.affiliation: National Center for Toxicological Research , Jefferson, Arkansas 72079, United States.
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Beland
authors.affiliation: Biotranex LLC , Monmouth Junction, New Jersey 08852, United States.
authors.forename: Lining
authors.initials: L
authors.lastname: Cai
authors.affiliation: National Center for Toxicological Research , Jefferson, Arkansas 72079, United States.
authors.forename: Peter P
authors.initials: PP
authors.lastname: Fu
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D008099:Liver / Q000187:drug effects*; D011506:Proteins / Q000737:chemistry*; D011763:Pyrrolizidine Alkaloids / Q000633:toxicity*; D051381:Rats; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D015415:Biomarkers; D011506:Proteins; D011763:Pyrrolizidine Alkaloids