Effet chez le porcelet d'une exposition à un régime co-contaminé en ...

TRAVAIL EXPERIMENTALtreated group there was no difference. Although not significant, it seems that an antagonisticinteraction between FB and DON affects the number of goblet cells as FB interfered with DON’seffect of decreasing the number of goblet cells.Controversial results have been reported with respect to intestinal proliferation in in vivo and invitro studies of mycotoxicosis. In this study, we have evaluated cell proliferation by counting mitoticfigures in intestinal crypts, which showed a significant decrease in the jejunum of the FB and DONtreatedgroups. Theumer et al. (2002) observed that subchronic experimental FB1 mycotoxicosisincreased the number of mitotic figures in rat intestinal crypts, while Obremski et al. (2008) observednumerous dividing cells within the glandular epithelium in pigs fed a diet containing DON,zearalenone and T-2 toxin. Using in vitro models, Bouhet et al. (2004) verified a decrease in theproliferation of undifferentiated porcine epithelial cells treated with FB1 due to a blockade in theG0/G1 cell cycle phase. Because DON acts as a protein synthesis inhibitor, it is expected that cellswith high turnover such as crypt enterocytes will be a target for the toxin’s action. Recently, it wasshown in Caco-2 cells that DON causes a concentration-dependent decrease in total protein contentassociated with a reduction in the incorporation of [3H]-leucine, demonstrating its inhibitory effecton protein synthesis (Van de Walle et al., 2010). The modes of action of FB and DON to inhibit cellproliferation are quite different. FB lead to accumulation of free sphingoid bases that are proapoptotic,cytotoxic and growth cell inhibitors (Lalles et al., 2010), while DON acts as a proteinsynthesis inhibitor.Mononuclear and eosinophil inflammatory infiltrate has been reported in FB mycotoxicosis inseveral species. In addition, proliferation of lymphoid nodules in the ileum and cecum was alsoobserved (Theumer et al., 2002; Piva et al., 2005). We have shown that the number of lymphocytesin the lamina propria decreased significantly in the jejunum of the treated groups, mainly in the DONtreatment. Studies of macrophages and lymphocytes have shown that the trichothecene-mediatedimmunosuppressive effect was associated with induction of apoptosis (Rocha et al., 2005). DONinitiates its toxic effects by inducing ribotoxic stress, which activates c-jun terminal kinase and p38mitogen-activated protein kinase, stimulating apoptosis. DON was particularly potent in this respect,elevating caspase levels more than twelvefold (Shifrin and Anderson, 1999). Because lymphoid cellsare constantly renewing, lymphocytes could be particularly sensitive to DON. It is interesting that ourresults show that even low doses of both mycotoxins induced a decrease in lymphocyte infiltration.This effect also occurred in the jejunum along with other histological alterations, supporting thefinding that this region is a main target for toxin action.In the present study, the chronic treatment of piglets with FB, DON or both by the oral routeinduced activation of the proinflammatory cytokine network in the intestine. Increases in the mRNA118