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Individual and combined toxicity of a mycotoxin, the deoxynivalenol and a trace metal, the cadmium on the intestine

Luo, Su. Individual and combined toxicity of a mycotoxin, the deoxynivalenol and a trace metal, the cadmium on the intestine. PhD, Pathologie, Toxicologie, Génétique et Nutrition, Institut National Polytechnique de Toulouse, 2019, 149 p.

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Abstract

Deoxynivalenol (DON) is a type B trichothecene mycotoxin mainly produced by Fusarium genus. It is one of the most prevalent mycotoxins widely found in cereals and cereal-derived products. Cadmium is a component of earth’s crust and also a common environmental pollutant. It is a nonessential trace metal and toxic for humans and animals health. Although the individual toxicity of DON and Cd has been well investigated, their combined effect is poorly studied. As intestine is the first organ targeted by food contaminants, the aim of this study is to explore the combined effect of DON and Cd on the intestinal barrier function using in vitro, in vivo and ex vivo models. In vitro, the human intestinal epithelail cells Caco-2 were treated with a series of concentrations of DON and Cd (0-30 μM) alone or in combination. The barrier function of Caco-2 cells was assessed through the measurement of transepithelial electrical resistance (TEER), paracellular permeability and junctional proteins. DON, Cd and DON+Cd mixture decreased the TEER and increased the paracellular permeability in a concentration-dependent manner. The abundance of junctional proteins E-cadherin and occludin was considerably reduced in cells exposed to DON, Cd and DON+Cd, while the expression of ZO-1, and claudin-3 and -4 remained unchanged. The mixture DON+Cd induced slightly higher or similar effects than the most toxic contaminant. In vivo, rats were exposed to DON-contaminated feed (8.2 mg/kg feed), and Cd-contaminated drinking water (5 mg/L) or to the mixture DON+Cd for 4 weeks. The results showed no effect on body weight gain during the experiment. Mild morphological damage characterized by edema in lamina propria and villi flattening and fusion was found in rat exposed to each contaminant. The lesional score of jejunum was higher in all the treated animals than that in control animals. A significant decrease of jejunal crypt depth was observed in rats exposed to DON, Cd and DON+Cd, whereas villi height remained unaffected. A lower immunostaining of E-cadherin in the jejunum of rats exposed to contaminants alone or in combination was also observed, whereas occludin was only decreased in rats exposed to DON and DON+Cd. As shown in vitro, in vivo exposure to both DON and Cd induced similar effects than the most toxic contaminant. Ex vivo, jejunal explants of pigs were exposed to DON (0-24 μM), Cd (0-96 μM) and in combination DON+Cd. DON alone and mixture DON+Cd stimulated immune response in jejunum by upregulating mRNA expression of IL-1, IL-1, IL- 8 and TNF- in a dose-dependent manner, while Cd alone did not affect these genes. Gene expression of metallothioneins (MTs) including MT1A and MT2A was dose-dependently upregulated by Cd alone and mixture, but not affected by DON alone. The upregulation of cytokine and MTs genes induced by DON+Cd was similar than by DON or Cd alone. In conclusion, both DON and Cd alter intestinal barrier function and the combined effect is similar with their individual effect. The effect of the mixture did not demonstrate any synergy, suggesting that regulation on individual contaminant is protective enough for consumers exposed to DON and Cd mixtures.

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
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Deposited On:24 Mar 2020 07:30

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