title: The mycotoxins deoxynivalenol and nivalenol show in vivo synergism on jejunum enterocytes apoptosis.
abstract: The mycotoxins deoxynivalenol (DON) and nivalenol (NIV), worldwide cereal contaminants, raise concerns for human and animal gut health, following exposure through contaminated food and feed. The aim of this work was to analyze the effects of DON and NIV, alone or associated, on the intestinal pig mucosa. Jejunal loops were used for testing DON and NIV individually and in combination (1:1) after a single exposure, for 24 h. For repeated exposure, piglets received a natural contaminated feed, with DON or with DON + NIV for 28 days. Histological investigations, proliferation and apoptosis assessments were conducted. Both experiments were concordant for the total-cell proliferation decreased at the villus tips after DON or DON + NIV at 10 μM acutely, or repeatedly, by 30-35% and 20-25%, respectively. In loops model, apoptotic enterocytes at villus tips increased dose-dependently after DON, NIV alone or DON + NIV in combination. The combination in loops at 10 μM showed higher effects on proliferation and apoptosis than DON alone, and synergism was shown for villus apoptotic enterocyte. These results are to be considered for NIV consumer risk assessment. Our results demonstrate the in vivo disruption of the intestinal balance proliferation/apoptosis explaining, at least partly, the disruption of intestinal barrier by these mycotoxins.
authors.affiliation: Université de Toulouse, Institut National Polytechnique-Ecole Nationale Vétérinaire (INP-ENVT), Unité Mixte de Recherche UMR 1331 Toxalim, Research Center in Food Toxicology, 23 chemin des Capelles, F-31300 Toulouse, France; INRA, UMR 1331 Toxalim, Research Center in Food Toxicology, 180 chemin de Tournefeuille F-31027 Toulouse, France; Faculty of Animal Science and Veterinary Medicine, Royal University of Agriculture, P.O. Box 2696, Phnom Penh, Cambodia.
authors.forename: Sophal
authors.initials: S
authors.lastname: Cheat
authors.affiliation: Université de Toulouse, Institut National Polytechnique-Ecole Nationale Vétérinaire (INP-ENVT), Unité Mixte de Recherche UMR 1331 Toxalim, Research Center in Food Toxicology, 23 chemin des Capelles, F-31300 Toulouse, France; INRA, UMR 1331 Toxalim, Research Center in Food Toxicology, 180 chemin de Tournefeuille F-31027 Toulouse, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Pinton
authors.affiliation: Université de Toulouse, Institut National Polytechnique-Ecole Nationale Vétérinaire (INP-ENVT), Unité Mixte de Recherche UMR 1331 Toxalim, Research Center in Food Toxicology, 23 chemin des Capelles, F-31300 Toulouse, France; INRA, UMR 1331 Toxalim, Research Center in Food Toxicology, 180 chemin de Tournefeuille F-31027 Toulouse, France.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Cossalter
authors.affiliation: Plate-forme CIRE Chirurgie et Imagerie pour la Recherche et l'Enseignement UMR 085 PRC, INRA, 37380 Nouzilly, France.
authors.forename: Juliette
authors.initials: J
authors.lastname: Cognie
authors.affiliation: ARVALIS - Institut du végétal, Pôle Valorisation Animale, Pouline 41100 Villerable, France.
authors.forename: Maria
authors.initials: M
authors.lastname: Vilariño
authors.affiliation: ARVALIS - Institut du végétal, Pôle Valorisation Animale, Pouline 41100 Villerable, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Callu
authors.affiliation: INP-ENVT, Université de Toulouse, F-31300 Toulouse, France; STROMALab UMR5273 UPS EFS INSERM U1031, 1 Avenue Jean Poulhes, 31403 Toulouse, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Raymond-Letron
authors.affiliation: Université de Toulouse, Institut National Polytechnique-Ecole Nationale Vétérinaire (INP-ENVT), Unité Mixte de Recherche UMR 1331 Toxalim, Research Center in Food Toxicology, 23 chemin des Capelles, F-31300 Toulouse, France; INRA, UMR 1331 Toxalim, Research Center in Food Toxicology, 180 chemin de Tournefeuille F-31027 Toulouse, France.
authors.forename: Isabelle P
authors.initials: IP
authors.lastname: Oswald
authors.affiliation: Université de Toulouse, Institut National Polytechnique-Ecole Nationale Vétérinaire (INP-ENVT), Unité Mixte de Recherche UMR 1331 Toxalim, Research Center in Food Toxicology, 23 chemin des Capelles, F-31300 Toulouse, France; INRA, UMR 1331 Toxalim, Research Center in Food Toxicology, 180 chemin de Tournefeuille F-31027 Toulouse, France. Electronic address: m.kolf-clauw@envt.fr.
authors.forename: Martine
authors.initials: M
authors.lastname: Kolf-Clauw
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D020895:Enterocytes / Q000187:drug effects*; D005260:Female; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D007583:Jejunum / Q000166:cytology* / Q000187:drug effects / Q000473:pathology; D008297:Male; D013552:Swine; D014255:Trichothecenes / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D014255:Trichothecenes; C038405:nivalenol; C007262:deoxynivalenol
keywords: Apoptosis; Fusariotoxins; Interaction; Intestinal mucosa; Loops