In vitro and in vivo effects of a mycotoxin, deoxynivalenol, and a trace metal, cadmium, alone or in a mixture on the intestinal barrier

霉菌毒素脱氧雪腐镰刀菌烯醇和痕量金属镉(单独或混合)对肠道屏障的体外和体内影响

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作者:Su Luo, Chloe Terciolo, Ana Paula F L Bracarense, Delphine Payros, Philippe Pinton, Isabelle P Oswald

Abstract

Deoxynivalenol (DON), one of the most widespread mycotoxins in Europe, and cadmium (Cd), a widespread environmental pollutant, are common food contaminants. They exert adverse effects on different organs including kidney, liver, and intestine. The intestine is a common target of DON and Cd when they are ingested. Most studies have focused on their individual effects whereas their combined toxicity has rarely been studied. The aim of this study was thus to evaluate their individual and combined effects on the intestinal barrier function in vitro and in vivo. In vitro, Caco-2 cells were treated with increasing concentrations of DON and Cd (1-30 μM). In vivo, Wistar rats were used as controls or exposed to DON contaminated feed (8.2 mg/kg feed), Cd-contaminated water (5 mg/l) or both for four weeks. In Caco-2 cells, DON, Cd and the DON+Cd mixture reduced transepithelial electrical resistance (TEER) and increased paracellular permeability in a dose-dependent manner. Impairment of the barrier function was associated with a decrease in the amount of E-cadherin and occludin after exposure to the two contaminants alone or combined. A decrease in E-cadherin expression was observed in rats exposed to the two contaminants alone or combined, whereas occludin expression only decreased in animals exposed to DON and DON+Cd. Jejunal crypt depth was reduced in rats exposed to DON or Cd, whereas villi height was not affected. In vitro and in vivo results showed that the effects of exposure to combined DON and Cd on the intestinal barrier function in the jejunum of Wistar rats and in the colorectal cancer cell line (Caco-2) was similar to the effects of each individual contaminant. This suggests that regulations for each individual contaminant are sufficiently protective for consumers.

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