title: 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.
abstract: 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 μM 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 ERK 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.
authors: INRA, UMR 1331, ToxAlim, Research Centre in Food Toxicology, F 31027 Toulouse, France.
authors: Joelma
authors: J
authors: Lucioli
authors: Philippe
authors: P
authors: Pinton
authors: Patrick
authors: P
authors: Callu
authors: Joëlle
authors: J
authors: Laffitte
authors: François
authors: F
authors: Grosjean
authors: Martine
authors: M
authors: Kolf-Clauw
authors: Isabelle P
authors: IP
authors: Oswald
authors: Ana Paula F R L
authors: AP
authors: Bracarense
mesh_terms: D000821:Animal Feed; D000826:Animal Testing Alternatives; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005506:Food Contamination; D007583:Jejunum / Q000187:drug effects* / Q000201:enzymology; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009919:Orchiectomy; D010766:Phosphorylation; D013552:Swine; D014255:Trichothecenes / Q000633:toxicity*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D014255:Trichothecenes; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; C007262:deoxynivalenol