title: Intestinal toxicity of the masked mycotoxin deoxynivalenol-3-β-D-glucoside.
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.
authors.affiliation: UMR-1331, Toxalim, Research Center in Food Toxicology, INRA, 180 chemin de Tournefeuille, 31027, Toulouse Cedex 3, France.|INP, UMR 1331, Toxalim, Université de Toulouse, Toulouse, France.|BIOMIN Research Center, Technopark 1, 3430, Tulln, Austria.
authors.forename: Alix
authors.initials: A
authors.lastname: Pierron
authors.affiliation: UMR-1331, Toxalim, Research Center in Food Toxicology, INRA, 180 chemin de Tournefeuille, 31027, Toulouse Cedex 3, France.|INP, UMR 1331, Toxalim, Université de Toulouse, Toulouse, France.
authors.forename: Sabria
authors.initials: S
authors.lastname: Mimoun
authors.affiliation: UMR-1331, Toxalim, Research Center in Food Toxicology, INRA, 180 chemin de Tournefeuille, 31027, Toulouse Cedex 3, France.|INP, UMR 1331, Toxalim, Université de Toulouse, Toulouse, France.|Lab. Patologia Animal, Universidade Estadual de Londrina, CP 6001, Londrina, Brazil.
authors.forename: Leticia S
authors.initials: LS
authors.lastname: Murate
authors.affiliation: UMR-1331, Toxalim, Research Center in Food Toxicology, INRA, 180 chemin de Tournefeuille, 31027, Toulouse Cedex 3, France.|INP, UMR 1331, Toxalim, Université de Toulouse, Toulouse, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Loiseau
authors.affiliation: UMR-1331, Toxalim, Research Center in Food Toxicology, INRA, 180 chemin de Tournefeuille, 31027, Toulouse Cedex 3, France.|INP, UMR 1331, Toxalim, Université de Toulouse, Toulouse, France.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Lippi
authors.affiliation: Lab. Patologia Animal, Universidade Estadual de Londrina, CP 6001, Londrina, Brazil.
authors.forename: Ana-Paula F L
authors.initials: AP
authors.lastname: Bracarense
authors.affiliation: UMR1388 Génétique, Physiologie et Systèmes d'Elevage, INRA, 31326, Castanet-Tolosan, France.|INPT ENSAT, UMR1388 Génétique, Physiologie et Systèmes d'Elevage, Université de Toulouse, 31326, Castanet-Tolosan, France.|INPT ENVT, UMR1388 Génétique, Physiologie et Systèmes d'Elevage, Université de Toulouse, 31076, Castanet-Tolosan, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Liaubet
authors.affiliation: BIOMIN Research Center, Technopark 1, 3430, Tulln, Austria.
authors.forename: Gerd
authors.initials: G
authors.lastname: Schatzmayr
authors.affiliation: Christian Doppler Laboratory for Mycotoxin Metabolism and Center for Analytical Chemistry, Department for Agrobiotechnology (IFA-Tulln), University of Natural Resources and Life Sciences, Vienna, Austria.
authors.forename: Franz
authors.initials: F
authors.lastname: Berthiller
authors.affiliation: BIOMIN Research Center, Technopark 1, 3430, Tulln, Austria.
authors.forename: Wulf-Dieter
authors.initials: WD
authors.lastname: Moll
authors.affiliation: UMR-1331, Toxalim, Research Center in Food Toxicology, INRA, 180 chemin de Tournefeuille, 31027, Toulouse Cedex 3, France. ioswald@toulouse.inra.fr.|INP, UMR 1331, Toxalim, Université de Toulouse, Toulouse, France. ioswald@toulouse.inra.fr.
authors.forename: Isabelle P
authors.initials: IP
authors.lastname: Oswald
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000235:genetics; D005506:Food Contamination / Q000032:analysis*; D005960:Glucosides / Q000633:toxicity*; D006801:Humans; D007583:Jejunum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D010458:Peptidyl Transferases / Q000378:metabolism; D011485:Protein Binding; D012270:Ribosomes / Q000187:drug effects / Q000201:enzymology; D013552:Swine; D059467:Transcriptome / Q000187:drug effects; D014255:Trichothecenes / Q000633:toxicity*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016207:Cytokines; D005960:Glucosides; D014255:Trichothecenes; C542050:deoxynivalenol-3-glucoside; D010458:Peptidyl Transferases; D048051:p38 Mitogen-Activated Protein Kinases; C007262:deoxynivalenol
keywords: Fusarium; Glucosylation; Gut; Modified mycotoxins; Trichothecenes; Wheat