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Study of the toxic effect of the estrogenic mycotoxin Zearalenone on the small intestine

Lahjouji, Tarek. Study of the toxic effect of the estrogenic mycotoxin Zearalenone on the small intestine. PhD, Pathologie, Toxicologie, Génétique et Nutrition, Institut National Polytechnique de Toulouse, 2021

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Abstract

Zearalenone (ZEN) is one of the stable mycotoxins produced by fungi of the genus Fusarium, which contaminate grain-based foods and animal feeds. Following oral exposure, ZEN is metabolized in various tissues, including the intestine. The major metabolites are -Zearalenol (- ZEL) and -Zearalenol (-ZEL). ZEN is known to have estrogenic effects due to its estrogen-like chemical structure, which allows it to interact directly with the estrogen receptors ER and ER. The reproductive effects of ZEN have been well elucidated in several species. However, the impact of ZEN on other organs is still poorly understood. As is the case for the intestine, which is the first organ affected by food contaminants. In the present study, and using a porcine jejunal explant model, we are studying the changes in gene expression and protein abundance induced by acute exposure to ZEN. Next, we explored the combined effect of ZEN and -ZEL on the gut in terms of additivity, synergy or antagonism, using an in vitro model, human intestinal epithelial cells Caco-2. The results indicate that ZEN can modulate the Wnt / - catenin signaling pathway and induce the expression of proliferation biomarkers. This is associated with an accumulation of ER in the gut, modulation of adipokine receptor expression and antimicrobial activity without inducing inflammation. We observed that ZEN and its metabolite -ZEL have a dose-dependent cytotoxic effect on Caco-2 intestinal epithelial cells. Our results also indicate a synergistic cytotoxic effect when the two toxins are present in a mixture. As a result, co-exposure to ZEN and -ZEL could result in a stronger effect than that resulting from exposure to each toxin alone. All our results clearly show that the intestine is a target for the mycotoxin ZEN, as well as the molecular mechanisms that explain these effects.

Item Type:PhD Thesis
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Institution:Université de Toulouse > Institut National Polytechnique de Toulouse - Toulouse INP (FRANCE)
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Research Director:
Oswald, Isabelle and Soler-Vasco, Laura
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Deposited On:19 Oct 2021 08:48

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