Preparation and Characterization of Cysteine Adducts of Deoxynivalenol

J Agric Food Chem. 2016 Jun 15;64(23):4777-85. doi: 10.1021/acs.jafc.6b01158. Epub 2016 Jun 3.

Abstract

Conjugation with the biologically relevant thiol glutathione is one of the metabolic pathways for the mycotoxin deoxynivalenol (DON) in wheat. The occurrence of putative DON-cysteine conjugates has also been shown in wheat, likely in part as a result of degradation of the glutathione conjugates. It was reported that thiols react in vitro with DON at two positions: reversibly at C-10 of the α,β-unsaturated ketone and irreversibly at C-13 of the epoxy group. We synthesized pure DON-cysteine adducts and made analytical standards using quantitative NMR experiments. Compounds were characterized using NMR and LC-HRMS/MS and tested in vitro for toxicity. Cysteine conjugates were much less toxic than DON at the same concentration, and LC-HRMS analysis demonstrated that there was no detectable metabolism of the conjugates in human monocytes or human macrophages.

Keywords: DON; ERETIC; HRMS; LC−MS; Michael adduct; NMR; qNMR; thiol.

MeSH terms

  • Cell Line
  • Chromatography, Liquid / methods
  • Culture Media / analysis
  • Culture Media / chemistry
  • Cysteine / analysis*
  • Cysteine / chemistry*
  • Cysteine / toxicity
  • Humans
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Mycotoxins / analysis
  • Oxidation-Reduction
  • Tandem Mass Spectrometry / methods
  • Trichothecenes / analysis*
  • Trichothecenes / chemistry*
  • Trichothecenes / toxicity
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Culture Media
  • Mycotoxins
  • Trichothecenes
  • Tumor Necrosis Factor-alpha
  • deoxynivalenol
  • Cysteine