Nivalenol and Deoxynivalenol affect rat intestinal epithelial cells: a concentration related study

The gastrointestinal tract integrity represents the first line of defence against ingested toxins. Nivalenol is a trichotecenes mycotoxin, frequent on cereals and processed grains, and its food and feed contamination is generally associated with that of Deoxynivalenol. Following their ingestion, intestinal epithelial cells result exposed to high concentrations of trichothecenes able to induce mycotoxicosis. Here we investigated the effects of Nivalenol and Deoxynivalenol on intestinal cells integrity using the not tumorigenic rat intestinal epithelial cell line (IEC-6). Both Nivalenol and Deoxynivalenol (5-80µM) significantly affected IEC-6 viability through a pro-apoptotic process which mainly involved (i) Bax induction; (ii) Bcl-2 inhibition and (iii) caspase-3 activation. Moreover, Nivalenol treatment induces in IEC-6 a significant arrest in cell cycle in G0/G1 and S phases associated to a decrease of G2 phase. Interestingly, Nivalenol and Deoxynivalenol at lower concentrations (0.1-2.5µM) have been able to modulate epithelial cell migration (restitution), the initial step of gastrointestinal wound healing, which normally occurs to maintain gut functions. The reduced restitution has been shown to be associated to alterations of connexin-43, focal adhesion kinase and cells actin remodelling. The range of the assayed Nivalenol or Deoxynivalenol concentrations is well in accordance with the mean estimated daily intake of consumers eating contaminated food. Thus our results further highlighted the risk assessment process associated also to low levels of these toxins.