title: Nivalenol and deoxynivalenol affect rat intestinal epithelial cells: a concentration related study.
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 G(0)/G(1) interphase and in the S phase, with a concomitant reduction in the fraction of cells in G(2). 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.
authors.affiliation: Department of Pharmaceutical and Biomedical Sciences, School of Pharmacy, University of Salerno, Fisciano, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bianco
authors.forename: Bianca
authors.initials: B
authors.lastname: Fontanella
authors.forename: Lorella
authors.initials: L
authors.lastname: Severino
authors.forename: Andrea
authors.initials: A
authors.lastname: Quaroni
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Autore
authors.forename: Stefania
authors.initials: S
authors.lastname: Marzocco
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018031:Connexin 43 / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D007422:Intestines / Q000187:drug effects*; D009183:Mycotoxins / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D014255:Trichothecenes / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D018031:Connexin 43; D009183:Mycotoxins; D019253:Proto-Oncogene Proteins c-bcl-2; D014255:Trichothecenes; D051028:bcl-2-Associated X Protein; C038405:nivalenol; D051416:Focal Adhesion Protein-Tyrosine Kinases; D053148:Caspase 3; C007262:deoxynivalenol