The food contaminant deoxynivalenol activates the mitogen activated protein kinases in the intestine: Interest of ex vivo models as an alternative to in vivo experiments

Joelma Lucioli (1, 2) , Philippe Pinton (3, 1) , Patrick Callu (4) , Joëlle J. Laffitte (3) , François Grosjean (4) , Martine Kolf-Klauw (1) , Isabelle P. Oswald (3, 1) , Ana Paula F.R.L. Bracarense (2)

1 UT3 - Université Toulouse III - Paul Sabatier
2 State University of Londrina = Universidade Estadual de Londrina
3 ToxAlim-BioToMyc - Biosynthèse & Toxicité des Mycotoxines
4 ARVALIS - Institut du végétal [Paris]

Trichothecenes induce changes in the intestinal barrier function through decreased expression of cell junction proteins and apoptosis of enterocytes. The mitogen activated protein kinases (MAPK) play an important role in the signaling pathways of cell turnover and differentiation. Using ex vivo and in vivo approaches, the purpose of this study was to investigate the ability of low doses of DON to induce histological changes in the intestine and to activate the MAPK ERK 1/2, p38 and JNK. Twelve weaning piglets received during four weeks a control diet or a DON-contaminated diet (2.3 mg DON/kg feed). Six weaning piglets were used to prepare jejunal explants (ex vivo model). Explants were exposed during 4 h to vehicle, 5 or 10 1.1 mu M DON. Intestinal changes were graded using a histological score. Pigs fed a DON-diet and explants exposed to DON showed a significant decrease in the jejunal score. In both models, the toxin significantly enhanced phosphorylation of ERR 1/2 and p38, whereas the increased phosphorylation of JNK was non significant. Taken together these results indicate that in vivo or ex vivo exposure of intestinal tissue to DON lead to similar intestinal lesions and activation of MAPK. These effects could impair the homeostasis of intestinal tissue in the aspects of barrier function and immune protection. The similarity of the in vivo and ex vivo results provides also strong evidence that the jejunal explant model is a good alternative for toxicological studies in intestinal tissue.

Mots clés: Trichothecenes; Pigs; MAPKinase; Mycotoxins; Intestine

Domaines: Sciences du Vivant [q-bio]

Joelma Lucioli, Philippe Pinton, Patrick Callu, Joëlle J. Laffitte, François Grosjean, et al.. The food contaminant deoxynivalenol activates the mitogen activated protein kinases in the intestine: Interest of ex vivo models as an alternative to in vivo experiments. Toxicon, 2013, 66, pp.31 - 36. ⟨10.1016/j.toxicon.2013.01.024⟩. ⟨hal-02652308⟩