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Co-exposure to low doses of the food contaminants deoxynivalenol and nivalenol has a synergistic inflammatory effect on intestinal explants

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Abstract

The global incidence of Fusarium head blight and attendant cereal grains multi-contamination by the trichothecene mycotoxins deoxynivalenol (DON) and nivalenol (NIV) are increasing as a possible result of climate change and inadequate agricultural practices. At the molecular level, these mycotoxins bind to the ribosome, activate the mitogen-activated protein kinase and induce a local and systemic inflammation. DON is of public health concern owing to the narrow margin between exposure and tolerable daily intake. The intestinal inflammatory response to DON, NIV and their mixture was analyzed to determine thresholds for their intestinal pro-inflammatory effects and characterize the type and magnitude of their interaction. Fully differentiated three-dimensional porcine jejunal explants were exposed to increasing doses of DON and NIV alone or in combination; the expression levels of IL-1α, IL-1β, IL-8, IL-17A and IL-22 were measured by RT-PCR. Doses as low as 0.16 µM DON or 0.73 µM NIV significantly increase the intestinal expression levels of the tested inflammation-related genes. These doses are lower than those previously reported for other intestinal toxicity endpoints. The combined pro-inflammatory activity of DON and NIV was synergistic for all the tested genes with combination index value range of 0.23–0.8. Our results indicate that (1) inflammation is a very sensitive endpoint for the intestinal toxicity of the trichothecenes and (2) co-exposure to DON and NIV has a greater inflammatory effect than induced by mycotoxins alone. This synergy should be taken into account considering the frequent co-occurrence of DON and NIV in the diet.

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Acknowledgements

The authors are grateful to Yannick LIPPI from the Toxalim Research Centre TRiX Facility for excellent technical assistance in data handling. This study was supported by Conseil Général de Midi-Pyrénées (Project No. 14051022 Tool4GutHealth) and Agence Nationale de la Recherche (Project ANR-10 CESA DON&Co and Project ANR-15-CE21-0001-02 CaDON). I. A. K. was supported by a doctoral fellowship from the Government of Republic of Benin.

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  1. Ting-Chao Chou

    Present address: PD Science LLC, Paramus, NJ, 07652-1754, USA

Authors and Affiliations

  1. Toxalim (Research Center in Food Toxicology), Université de Toulouse, INRA, ENVT, INP-PURPAN, UPS 180 Chemin de Tournefeuille, BP93173, 31027, Toulouse Cedex 03, France

    Imourana Alassane-Kpembi, Olivier Puel, Philippe Pinton, Anne-Marie Cossalter & Isabelle P. Oswald

  2. Hôpital d’Instruction des Armées, Camp Guézo, 01BP517, Cotonou, Bénin

    Imourana Alassane-Kpembi

  3. Molecular Pharmacology and Chemistry Program, Memorial Sloan-Kettering Cancer Center, New York, NY, 10065, USA

    Ting-Chao Chou

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  1. Imourana Alassane-Kpembi
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Alassane-Kpembi, I., Puel, O., Pinton, P. et al. Co-exposure to low doses of the food contaminants deoxynivalenol and nivalenol has a synergistic inflammatory effect on intestinal explants. Arch Toxicol 91, 2677–2687 (2017). https://doi.org/10.1007/s00204-016-1902-9

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