Abstract
The integrity of the gastrointestinal tract represents a crucial first level defence against ingested toxins. Among them, Nivalenol is a trichotecenes mycotoxin frequently found on cereals and processed grains; when it contaminates human food and animal feed it is often associated with another widespread contaminant, Deoxynivalenol. Following their ingestion, intestinal epithelial cells are exposed to concentrations of these trichothecenes high enough to cause mycotoxicosis. In this study we have investigated the effects of Nivalenol and Deoxynivalenol on intestinal cells in an in vitro model system utilizing the non-tumorigenic rat intestinal epithelial cell line IEC-6. Both Nivalenol and Deoxynivalenol (5–80 µM) significantly affected IEC-6 viability through a pro-apoptotic process which mainly involved the following steps: (i) Bax induction; (ii) Bcl-2 inhibition, and (iii) caspase-3 activation. Moreover, treatment with Nivalenol produced a significant cell cycle arrest of IEC-6 cells, primarily at the G0/G1 interphase and in the S phase, with a concomitant reduction in the fraction of cells in G2. Interestingly, when administered at lower concentrations (0.1–2.5 µM), both Nivalenol and Deoxynivalenol affected epithelial cell migration (restitution), representing the initial step in gastrointestinal wound healing in the gut. This reduced motility was associated with significant remodelling of the actin cytoskeleton, and changes in expression of connexin-43 and focal adhesion kinase. The concentration range of Nivalenol or Deoxynivalenol we have tested is comparable with the mean estimated daily intake of consumers eating contaminated food. Thus, our results further highlight the risks associated with intake of even low levels of these toxins.
Highlights
Mycotoxins are food contaminants produced by secondary metabolism of fungi found primarily in cereal grains and derived products
NIV- and DON-induced Apoptosis in Intestinal epithelial cells (IECs)-6 Cells In order to investigate the mechanism(s) underlying cell observed decrease in cell viability observed in NIV- or DONtreated IEC-6 cells a cytofluorimetric analysis was performed by incubating IEC-6 with graded concentrations of each mycotoxin (0.5–80 mM) for 24h
Our results indicate that both NIV and DON significantly (P,0,001) induced apoptosis in IEC-6, in a concentration-dependent manner, from 5 mM and 10 mM for NIV- or DON-treated cells respectively; whereas any apoptotic effect have been observed at the lowest concentrations tested (2.5 mM for NIV and 5 mM for DON)
Summary
Mycotoxins are food contaminants produced by secondary metabolism of fungi found primarily in cereal grains and derived products. A data collection on the occurrence of Fusarium toxins in food in the European Union showed a 57% incidence of positive samples for deoxynivalenol (DON) and 16% for nivalenol (NIV), out of several thousands of samples analysed [5]. Due to their toxic properties and their high stability to heat treatment, the presence of these mycotoxins in the food chain is potentially hazardous to health [6,7,8,9]
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