Mycotoxins modify the barrier function of Caco-2 cells through differential gene expression of specific claudin isoforms: Protective effect of illite mineral clay

Toxicology. 2016 Apr 15:353-354:21-33. doi: 10.1016/j.tox.2016.05.003. Epub 2016 May 3.

Abstract

Aflatoxin B1 (AFB1), fumonisin B1 (FB1), ochratoxin A (OTA) and T-2 toxin (T2) are mycotoxins that commonly contaminate the food chain and cause various toxicological effects. Their global occurrence is regarded as an important risk factor for human and animal health. In this study, the results demonstrate that, in human Caco-2 cells, AFB1, FB1, OTA and T2 origin cytotoxic effects, determining cell viability through MTT assay and LDH leakage, and decrease trans-epithelial electrical resistance (TEER). The decrease in barrier properties is concomitant with a reduction in the expression levels of the tight junction constituents claudin-3, claudin-4 and occludin. The protective effect of mineral clays (diosmectite, montmorillonite and illite) on alterations in cell viability and epithelial barrier function induced by the mycotoxins was also evaluated. Illite was the best clay to prevent the mycotoxin effects. Illite plus mycotoxin co-treatment completely abolished AFB1 and FB1-induced cytotoxicity. Also, the decreases in the gene expression of claudins and the reduction of TEER induced by mycotoxins were reversed by the illite plus mycotoxin co-treatment. In conclusion, these results demonstrated that mycotoxins AFB1, FB1, T2 and OTA disrupt the intestinal barrier permeability by a mechanism involving reduction of claudin isoform expressions, and illite counteracts this disruption.

Keywords: Barrier function; Caco-2-cells; Cytotoxicity; Illite; Mycotoxins; Tight junctions.

Publication types

  • Comparative Study

MeSH terms

  • Antidotes / pharmacology
  • Bentonite / pharmacology*
  • Caco-2 Cells
  • Cell Survival / drug effects
  • Claudin-3 / genetics
  • Claudin-4 / genetics
  • Electric Impedance
  • Gene Expression Regulation / drug effects*
  • Humans
  • Minerals / pharmacology*
  • Mycotoxins / toxicity*
  • Occludin / genetics
  • Permeability
  • Silicates / pharmacology*
  • Tight Junctions / drug effects

Substances

  • Antidotes
  • Claudin-3
  • Claudin-4
  • Minerals
  • Mycotoxins
  • Occludin
  • Silicates
  • illite
  • Bentonite
  • Smectite