Deoxynivalenol Impairs Hepatic and Intestinal Gene Expression of Selected Oxidative Stress, Tight Junction and Inflammation Proteins in Broiler Chickens, but Addition of an Adsorbing Agent Shifts the Effects to the Distal Parts of the Small Intestine

Osselaere, Ann; Santos, Regiane R.; Hautekiet, Veerle; Backer, Patrick De; Chiers, Koen; Ducatelle, Richard; Croubels, Siska

doi:10.1371/journal.pone.0069014

Cited by 144 publications

(143 citation statements)

References 52 publications

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“…Pig can be regarded as a good model of extrapolation to humans (Helke and Swindle 2013). DON induces morphological injury (Osselaere et al 2013) and inflammation on porcine jejunum explants (Cano et al 2013). Cytokines and chemokines are sensitive biomarkers for DON exposure (Pestka 2010;Wu et al 2014a).…”

Section: Discussionmentioning

confidence: 99%

“…In vivo, the conversion of D3G to its toxic aglycone may occur in the distal part of the gut, while ingested DON is absorbed in the proximal part of the small intestine (Maresca 2013). Hence, ingestion of D3G-contaminated food might lead to a release of DON in the distal part of intestine, shifting the toxic effect of D3G in the distal part of the intestine as already described for ingestion of DON-contaminated food in the presence of this adsorbing agent (Osselaere et al 2013). Nevertheless, acute ingestion of high doses of D3G does not induce inflammatory reaction in mice and mink (Wu et al 2014a) nor emetic effect in mink (Wu et al 2014b).…”

Section: Figmentioning

confidence: 93%

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Intestinal toxicity of the masked mycotoxin deoxynivalenol-3-β-d-glucoside

et al. 2015

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Natural food contaminants such as mycotoxins are an important problem for human health. Deoxynivalenol (DON) is one of the most common mycotoxins detected in cereals and grains. Its toxicological effects mainly concern the immune system and the gastrointestinal tract. This toxin is a potent ribotoxic stressor leading to MAP kinase activation and inflammatory response. DON frequently co-occurs with its glucosylated form, the masked mycotoxin deoxynivalenol-3-β-D-glucoside (D3G). The toxicity of this later compound remains unknown in mammals. This study aimed to assess the ability of D3G to elicit a ribotoxic stress and to induce intestinal toxicity. The toxicity of D3G and DON (0-10 µM) was studied in vitro, on the human intestinal Caco-2 cell line, and ex vivo, on porcine jejunal explants. First, an in silico analysis revealed that D3G, contrary to DON, was unable to bind to the A-site of the ribosome peptidyl transferase center, the main targets for DON toxicity. Accordingly, D3G did not activate JNK and P38 MAPKs in treated Caco-2 cells and did not alter viability and barrier function on cells, as measured by the trans-epithelial electrical resistance. Treatment of intestinal explants for 4 h with 10 µM DON induced morphological lesions and up-regulated the expression of pro-inflammatory cytokines as measured by qPCR and pan-genomic microarray analysis. By contrast, expression profile of D3G-treated explants was similar to that of controls, and these explants did not show histomorphology alteration. In conclusion, our data demonstrated that glucosylation of DON suppresses its ability to bind to the ribosome and decreases its intestinal toxicity.

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Section: Discussionmentioning

confidence: 99%

Section: Figmentioning

confidence: 93%

Intestinal toxicity of the masked mycotoxin deoxynivalenol-3-β-d-glucoside

et al. 2015

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“…Administration of higher doses can offer a possibility, but can lead to higher risks for acute mycotoxicosis. On the other hand, plasma or blood concentrations of the tested parent toxins and their main reported metabolites as stated by the EFSA (2011) cannot be used as biomarkers to test the efficacy of mycotoxin detoxifiers in broilers, when maximum recommended levels in feed are respected (Osselaere et al, 2013b).…”

Section: Mycotoxin Combinationsmentioning

confidence: 99%

In vivo toxicity studies of fusarium mycotoxins in the last decade: A review

Escrivá

Font

Manyes

2015

Food and Chemical Toxicology

310

203

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“…A significant reduction of villus height, villus surface area and muscularis thickness in the jejunum was also observed after feeding of naturally contaminated grains with DON (1 or 5 mg kg –1 feed) (Awad et al ., ). Data reported by others also indicated that the feeding of cereals naturally contaminated with DON (7.54 mg kg –1 diet) for 3 weeks resulted in a decreased villus length and crypt depth in the duodenum and jejunum of broiler chickens (Osselaere et al ., ). Girgis et al .…”

Section: Introductionmentioning

confidence: 99%

Impacts of the feed contaminant deoxynivalenol on the intestine of monogastric animals: poultry and swine

Ghareeb

Awad

Böhm

et al. 2014

J of Applied Toxicology

142

111

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Deoxynivalenol (DON) is one of the most prevalent cereal contaminants with major public health concerns owing to its high toxigenic potentials. Once ingested, DON first and foremost targets epithelial cells of the gastrointestinal tract, whose proper functioning, as the first line of defence, is of paramount importance for the host's health. Emerging evidences, summarized in this article, suggest that DON produces its toxicity primarily via activation of the mitogen-activated protein kinases (MAPKs) signalling pathway and alteration in the expression of genes responsible for key physiological and immunological functions of the intestinal tissue of chickens and pigs. The activation of MAPKs signalling cascade results in disruption of the gut barrier function and an increase in the permeability by reducing expression of the tight junction proteins. Exposure to DON also down-regulates the expression of multiple transporter systems in the enterocytes with subsequent impairment of the absorption of key nutrients. Other major intestinal cytotoxic effects of DON described herein are modulation of mucosal immune responses, leading to immunosupression or stimulation of local immune cells and cytokine release, and also facilitation of the persistence of intestinal pathogens in the gut. Both of the last events potentiate enteric infections and local inflammation in pigs and poultry, rendering enterocytes and the host more vulnerable to luminal toxic compounds. This review highlights the cytotoxic risks associated with the intake of even low levels of DON and also identifies gaps of knowledge that need to be addressed by future research.

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Deoxynivalenol Impairs Hepatic and Intestinal Gene Expression of Selected Oxidative Stress, Tight Junction and Inflammation Proteins in Broiler Chickens, but Addition of an Adsorbing Agent Shifts the Effects to the Distal Parts of the Small Intestine

Cited by 144 publications

References 52 publications

Intestinal toxicity of the masked mycotoxin deoxynivalenol-3-β-d-glucoside

Intestinal toxicity of the masked mycotoxin deoxynivalenol-3-β-d-glucoside

In vivo toxicity studies of fusarium mycotoxins in the last decade: A review

Impacts of the feed contaminant deoxynivalenol on the intestine of monogastric animals: poultry and swine

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