Blood Pyrrole-Protein Adducts--A Biomarker of Pyrrolizidine Alkaloid-Induced Liver Injury in Humans

J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2015;33(4):404-21. doi: 10.1080/10590501.2015.1096882.

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.

Keywords: hepatic sinusoidal obstruction syndrome; hepatotoxicity; pyrrole-protein adducts; pyrrolizidine alkaloids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Animals
  • Biomarkers / blood*
  • Chemical and Drug Induced Liver Injury / diagnosis*
  • Chromatography, High Pressure Liquid
  • Female
  • Hepatic Veno-Occlusive Disease / blood*
  • Humans
  • Male
  • Middle Aged
  • Pyrroles / blood*
  • Pyrroles / chemistry
  • Pyrrolizidine Alkaloids / blood*
  • Pyrrolizidine Alkaloids / chemistry
  • Pyrrolizidine Alkaloids / metabolism
  • Rats
  • Toxicity Tests
  • Toxins, Biological / chemistry
  • Toxins, Biological / metabolism

Substances

  • Biomarkers
  • Pyrroles
  • Pyrrolizidine Alkaloids
  • Toxins, Biological