Effects of deoxynivalenol (DON) and its microbial biotransformation product deepoxy-deoxynivalenol (DOM-1) on a trout, pig, mouse, and human cell line

Mycotoxin Res. 2017 Nov;33(4):297-308. doi: 10.1007/s12550-017-0289-7. Epub 2017 Jul 24.

Abstract

Deoxynivalenol (DON), a trichothecene produced by various Fusarium species, is one of the most prevalent food- and feed-associated mycotoxins. The effects of DON and deepoxy-deoxynivalenol (DOM-1) were assessed in five different cell lines from different tissues and species starting from the first line of defense, the trout gill (RTgill-W1) and pig intestinal cells (IPEC-1 and IPEC-J2) over immune cells, as second line of defense (mouse macrophages RAW 264.7) to human liver cells (HepG2). Viability was assessed with a WST-1 assay, except for RTgill-W1, where a neutral red (NR) and sulforhodamine B (SRB) assay was performed. Additionally, more sensitive parameters, such as interleukin-, nitric oxide (NO)-, and albumin-release were determined. Viability was affected by DON at concentrations starting at 10 μmol/L (RTgill-W1), 0.9 μmol/L (IPEC-1), 3.5 μmol/L (IPEC-J2), and 0.9 μmol/L (HepG2), whereas DOM-1 did not have such an effect. Additionally, NO was decreased (0.84 μmol/L DON), whereas interleukin (IL)-6 was increased (0.42 μmol/L DON) in lipopolysaccharide (LPS)-stimulated DON-, but not DOM-1-treated RAW cells. Tumor necrosis factor (TNF)-α release, however, was not affected. Interestingly, albumin secretion of HepG2 cells was decreased by both DON and DOM-1 but at a much higher concentration for DOM-1 (228 versus 0.9 μmol/L for DON). 98.9% of DOM-1 was retrieved by liquid chromatography tandem mass spectrometry at the end of the experiment, proving its stability. In this study, IL-6 was the most sensitive parameter, followed by NO and albumin release and viability for HepG2 and IPEC-1.

Keywords: Cell culture; Cell lines; Contamination; Cytotoxicity; Feedstuff; Fish; In vitro; Metabolite; Toxicity; Transformation.

MeSH terms

  • Animals
  • Biotransformation
  • Cell Line
  • Cell Survival / drug effects
  • Chromatography, Liquid
  • Cytokines / analysis
  • Humans
  • Mice
  • Mycotoxins / metabolism
  • Mycotoxins / pharmacology*
  • Swine
  • Tandem Mass Spectrometry
  • Trichothecenes / metabolism
  • Trichothecenes / pharmacology*
  • Trout

Substances

  • Cytokines
  • Mycotoxins
  • Trichothecenes
  • deepoxy-deoxynivalenol
  • deoxynivalenol