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Intestinal toxicity of the masked mycotoxin deoxynivalenol-3-β-D-glucoside.
- Source :
-
Archives of toxicology [Arch Toxicol] 2016 Aug; Vol. 90 (8), pp. 2037-46. Date of Electronic Publication: 2015 Sep 24. - Publication Year :
- 2016
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Abstract
- 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.
- Subjects :
- Animals
Caco-2 Cells
Cell Culture Techniques
Cell Survival drug effects
Cytokines genetics
Humans
Jejunum metabolism
Jejunum pathology
MAP Kinase Signaling System drug effects
Peptidyl Transferases metabolism
Protein Binding
Ribosomes drug effects
Ribosomes enzymology
Swine
Transcriptome drug effects
p38 Mitogen-Activated Protein Kinases metabolism
Food Contamination analysis
Glucosides toxicity
Jejunum drug effects
Trichothecenes toxicity
Subjects
Details
- Language :
- English
- ISSN :
- 1432-0738
- Volume :
- 90
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Archives of toxicology
- Publication Type :
- Academic Journal
- Accession number :
- 26404761
- Full Text :
- https://doi.org/10.1007/s00204-015-1592-8