Protein tyrosine adduct in humans self-poisoned by chlorpyrifos

Bin Li, Peter Eyer, Michael Eddleston, Wei Jiang, Lawrence M. Schopfer, Oksana Lockridge

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Studies of human cases of self-inflicted poisoning suggest that chlorpyrifos oxon reacts not only with acetylcholinesterase and butyrylcholinesterase but also with other blood proteins. A favored candidate is albumin because in vitro and animal studies have identified tyrosine 411 of albumin as a site covalently modified by organophosphorus poisons. Our goal was to test this proposal in humans by determining whether plasma from humans poisoned by chlorpyrifos has adducts on tyrosine. Plasma samples from 5 self-poisoned humans were drawn at various time intervals after ingestion of chlorpyrifos for a total of 34 samples. All 34 samples were analyzed for plasma levels of chlorpyrifos and chlorpyrifos oxon (CPO) as a function of time post-ingestion. Eleven samples were analyzed for the presence of diethoxyphosphorylated tyrosine by mass spectrometry. Six samples yielded diethoxyphosphorylated tyrosine in pronase digests. Blood collected as late as 5. days after chlorpyrifos ingestion was positive for CPO-tyrosine, consistent with the 20-day half-life of albumin. High plasma CPO levels did not predict detectable levels of CPO-tyrosine. CPO-tyrosine was identified in pralidoxime treated patients as well as in patients not treated with pralidoxime, indicating that pralidoxime does not reverse CPO binding to tyrosine in humans. Plasma butyrylcholinesterase was a more sensitive biomarker of exposure than adducts on tyrosine. In conclusion, chlorpyrifos oxon makes a stable covalent adduct on the tyrosine residue of blood proteins in humans who ingested chlorpyrifos.

Original languageEnglish (US)
Pages (from-to)215-225
Number of pages11
JournalToxicology and Applied Pharmacology
Volume269
Issue number3
DOIs
StatePublished - Jun 15 2013

Keywords

  • Albumin
  • Butyrylcholinesterase
  • Chlorpyrifos
  • Diethoxyphosphorylated tyrosine
  • Mass spectrometry
  • Poisoned patients

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

Fingerprint Dive into the research topics of 'Protein tyrosine adduct in humans self-poisoned by chlorpyrifos'. Together they form a unique fingerprint.

  • Cite this