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Sergent T, Parys M, Garsou S, Pussemier L, Schneider YJ,
Larondelle Y.
Vomitoxin (deoxynivalenol) (DON)
transport across human intestinal Caco-2 cells and its effects
on cellular metabolism at realistic intestinal concentrations.
Toxicol Lett. 2006 Jul 1;164(2):167-76.
Laboratoire de Biochimie Cellulaire, Croix du Sud, 5,
Institut des Sciences de la Vie & Université Catholique de
Louvain, B-1348 Louvain-la-Neuve, Belgium.
Deoxynivalenol (DON) is a mycotoxin of the trichothecenes family
to which human exposure levels can be high. Epidemiological
studies suggest a link between DON and gastrointestinal illness.
We investigated the interaction of DON with Caco-2 cells, a
widely used in vitro model of the human intestinal barrier. The
apical to basolateral (absorption) and basolateral to apical
(excretion) transports of DON were found strictly proportional
to both the initial concentration and the duration of the
incubation. The absorption and excretion mean rates were similar
to those of mannitol and were increased in the presence of EGTA,
a calcium chelator. These data suggest that DON crosses the
intestinal mucosa by a paracellular pathway through the tight
junctions although some passive transcellular diffusion may not
be ruled out. The DON transport was not affected by
P-glycoprotein (PgP) or multidrug resistance-associated proteins
(MRPs) inhibitors. A prolonged exposure to DON provokes the
phosphorylation of the mitogen-activated protein kinases (MAPKs)
Erk1/2, p38 and SAPK/JNK, as well as a decrease of the
transepithelial resistance, suggesting that DON could trigger
intestinal inflammation. These data imply that a chronic
exposure to DON contaminated foods may negatively affect human
health by altering the intestinal mucosa integrity and by
inducing the MAPKs implicated in inflammation.
PMID: 16442754
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