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

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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.

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Acknowledgments

The authors thank A.M. Cossalter, J. Laffitte and P. Pinton, INRA Toxalim, for sample collection and western experiments. Thanks are also due to R. Hines, BIOMIN, for language editing, and to P. Pinton and I. Alassane-Kpembi for critical reading of the manuscript. A. Pierron and L.S. Murate were supported by fellowship from CIFRE (2012/0572, jointly financed by the BIOMIN Holding GmbH, Association Nationale de la Recherche Technique and INRA) and CAPES (Brazil), respectively. The Austrian Federal Ministry of Science, Research and Economy, the Austria National Foundation for Research, Technology and Development and BIOMIN Holding GmbH are acknowledged for funding the Christian Doppler Laboratory for Mycotoxin Metabolism. The enzymatic production of D3G was performed within the Vienna Science and Technology Fund project WWTF LS12-012 by Dr. Herbert Michlmayr and Prof. Gerhard Adam.

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    Authors and Affiliations

    1. UMR-1331, Toxalim, Research Center in Food Toxicology, INRA, 180 chemin de Tournefeuille, 31027, Toulouse Cedex 3, France

      Alix Pierron, Sabria Mimoun, Leticia S. Murate, Nicolas Loiseau, Yannick Lippi & Isabelle P. Oswald

    2. INP, UMR 1331, Toxalim, Université de Toulouse, Toulouse, France

      Alix Pierron, Sabria Mimoun, Leticia S. Murate, Nicolas Loiseau, Yannick Lippi & Isabelle P. Oswald

    3. BIOMIN Research Center, Technopark 1, 3430, Tulln, Austria

      Alix Pierron, Gerd Schatzmayr & Wulf-Dieter Moll

    4. Lab. Patologia Animal, Universidade Estadual de Londrina, CP 6001, Londrina, Brazil

      Leticia S. Murate & Ana-Paula F. L. Bracarense

    5. UMR1388 Génétique, Physiologie et Systèmes d’Elevage, INRA, 31326, Castanet-Tolosan, France

      Laurence Liaubet

    6. INPT ENSAT, UMR1388 Génétique, Physiologie et Systèmes d’Elevage, Université de Toulouse, 31326, Castanet-Tolosan, France

      Laurence Liaubet

    7. INPT ENVT, UMR1388 Génétique, Physiologie et Systèmes d’Elevage, Université de Toulouse, 31076, Castanet-Tolosan, France

      Laurence Liaubet

    8. 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

      Franz Berthiller

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    Alix Pierron and Sabria Mimoun have contributed equally to this work.

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    Pierron, A., Mimoun, S., Murate, L.S. et al. Intestinal toxicity of the masked mycotoxin deoxynivalenol-3-β-d-glucoside. Arch Toxicol 90, 2037–2046 (2016). https://doi.org/10.1007/s00204-015-1592-8

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