Archives of Toxicology

, Volume 92, Issue 11, pp 3381–3389 | Cite as

Deepoxy-deoxynivalenol retains some immune-modulatory properties of the parent molecule deoxynivalenol in piglets

  • Alix Pierron
  • Ana Paula F. L. Bracarense
  • Anne-Marie Cossalter
  • Joëlle Laffitte
  • Heidi E. Schwartz-Zimmermann
  • Gerd Schatzmayr
  • Philippe Pinton
  • Wulf-Dieter Moll
  • Isabelle P. Oswald


Deoxynivalenol (DON) is the most abundant trichothecene in food and feed. It causes both acute and chronic disorders of the human and animal intestine, liver and the immune system. The structural basis for the toxicity of DON has not been fully elucidated. Using the pig as a target and a model species for human, the toxicity of DON and its deepoxy-metabolite (DOM-1) was compared. Animals were exposed by gavage to 1 and 0.5 nmol toxin/kg b.w./day for 2 and 3 weeks respectively. Whatever the dose/duration, DOM-1 was less toxic than DON in terms of weight gain and emesis. In the 3-week experiment, animals were vaccinated with ovalbumin, and their immune response was analyzed in addition to tissue morphology, biochemistry and hematology. DON impaired the morphology of the jejunum and the ileum, reduced villi height, decreased E-cadherin expression and modified the intestinal expression of cytokines. Similarly, DON induced hepatotoxicity as indicated by the lesion score and the blood biochemistry. By contrast, DOM-1 only induced minimal intestinal toxicity and did not trigger hepatotoxicity. As far as the immune response was concerned, the effects of ingesting DOM-1 were similar to those caused by DON, as measured by histopathology of lymphoid organs, PCNA expression and the specific antibody response. Taken together, these data demonstrated that DOM-1, a microbial detoxification product of DON, was not toxic in the sensitive pig model but retained some immune-modulatory properties of DON, especially its ability to stimulate a specific antibody response during a vaccination protocol.


Modified mycotoxins Epoxy group In vivo Immune response Pig 



A. Pierron was supported by fellowship from CIFRE (2012/0572, jointly financed by the BIOMIN Holding GmbH, Association Nationale de la Recherche Technique and INRA). The authors thank Drs. Alassane-Kpembi and Payros for helpful discussion.

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest during experimental work reported here.

Supplementary material

204_2018_2293_MOESM1_ESM.docx (452 kb)
Supplementary material 1 (DOCX 453 KB)

Supplementary material 2 (MP4 146153 KB)


  1. Akbari P, Braber S, Gremmels H, Koelink PJ, Verheijden KA, Garssen J et al (2014) Deoxynivalenol: a trigger for intestinal integrity breakdown. FASEB J 28:2414–2429. CrossRefPubMedGoogle Scholar
  2. Alassane-Kpembi I, Gerez JR, Cossalter AM, Neves M, Laffitte J, Naylies C et al (2017a) Intestinal toxicity of the type B trichothecene mycotoxin fusarenon-X: whole transcriptome profiling reveals new signaling pathways. Sci Rep 7:7530. CrossRefPubMedPubMedCentralGoogle Scholar
  3. Alassane-Kpembi I, Puel O, Pinton P, Cossalter AM, Chou TC, Oswald IP (2017b) 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. CrossRefPubMedGoogle Scholar
  4. Awad WA, Ghareeb K, Dadak A, Hess M, Bohm J (2014) Single and combined effects of deoxynivalenol mycotoxin and a microbial feed additive on lymphocyte DNA damage and oxidative stress in broiler chickens. PLoS One 9:e88028. CrossRefPubMedPubMedCentralGoogle Scholar
  5. Bracarense AP, Lucioli J, Grenier B, Drociunas Pacheco G, Moll WD, Schatzmayr G et al (2012) Chronic ingestion of deoxynivalenol and fumonisin, alone or in interaction, induces morphological and immunological changes in the intestine of piglets. Br J Nutr 107:1776–1786. CrossRefPubMedGoogle Scholar
  6. Chen SS, Li YH, Lin MF (2017) Chronic exposure to the fusarium mycotoxin deoxynivalenol: impact on performance, immune organ, and intestinal integrity of slow-growing chickens. Toxins 9:334. CrossRefPubMedCentralGoogle Scholar
  7. Devriendt B, Gallois M, Verdonck F, Wache Y, Bimczok D, Oswald IP et al (2009) The food contaminant fumonisin B(1) reduces the maturation of porcine CD11R1(+) intestinal antigen presenting cells and antigen-specific immune responses, leading to a prolonged intestinal ETEC infection. Vet Res 40:40. CrossRefPubMedPubMedCentralGoogle Scholar
  8. EFSA (2017) Scientific opinion on the risks to human and animal health related to the presence of deoxynivalenol and its acetylated and modified forms in food and feed. EFSA J 15:4718. CrossRefGoogle Scholar
  9. Gerez JR, Desto SS, Bracarense A (2016) Deoxynivalenol induces toxic effects in the ovaries of pigs: an ex vivo approach. Theriogenology 90:94–100. CrossRefPubMedGoogle Scholar
  10. Ghareeb K, Awad WA, Bohm J (2012) Ameliorative effect of a microbial feed additive on infectious bronchitis virus antibody titer and stress index in broiler chicks fed deoxynivalenol. Poult Sci 91:800–807. CrossRefPubMedGoogle Scholar
  11. Ghareeb K, Awad WA, Bohm J, Zebeli Q (2015) Impacts of the feed contaminant deoxynivalenol on the intestine of monogastric animals: poultry and swine. J Appl Toxicol 35:327–337. CrossRefPubMedGoogle Scholar
  12. Girish CK, Smith TK, Boermans HJ, Anil Kumar P, Girgis GN (2010) Effects of dietary Fusarium mycotoxins on intestinal lymphocyte subset populations, cell proliferation and histological changes in avian lymphoid organs. Food Chem Toxicol 48:3000–3007. CrossRefPubMedGoogle Scholar
  13. Grenier B, Bracarense AP, Schwartz HE, Trumel C, Cossalter AM, Schatzmayr G et al (2012) The low intestinal and hepatic toxicity of hydrolyzed fumonisin B(1) correlates with its inability to alter the metabolism of sphingolipids. Biochem Pharmacol 83:1465–1473. CrossRefPubMedGoogle Scholar
  14. Grenier B, Bracarense AP, Schwartz HE, Lucioli J, Cossalter AM, Moll WD et al (2013) Biotransformation approaches to alleviate the effects induced by fusarium mycotoxins in swine. J Agric Food Chem 61:6711–6719. CrossRefPubMedGoogle Scholar
  15. Guerrero-Netro HM, Estienne A, Chorfi Y, Price CA (2017) The mycotoxin metabolite deepoxy-deoxynivalenol increases apoptosis and decreases steroidogenesis in bovine ovarian theca cells. Biol Reprod 97:746–757. CrossRefPubMedGoogle Scholar
  16. Helke KL, Swindle MM (2013) Animal models of toxicology testing: the role of pigs. Expert Opin Drug Metab Toxicol 9:127–139. CrossRefPubMedGoogle Scholar
  17. Karlovsky P (2011) Biological detoxification of the mycotoxin deoxynivalenol and its use in genetically engineered crops and feed additives. Appl Microbiol Biotechnol 91:491–504. CrossRefPubMedPubMedCentralGoogle Scholar
  18. Li XZ, Zhu C, de Lange CF, Zhou T, He J, Yu H et al (2011) Efficacy of detoxification of deoxynivalenol-contaminated corn by Bacillus sp. LS100 in reducing the adverse effects of the mycotoxin on swine growth performance. Food Addit Contam Part A 28:894–901. CrossRefGoogle Scholar
  19. Liao Y, Peng Z, Chen L, Nussler AK, Liu L, Yang W (2018) Deoxynivalenol, gut microbiota and immunotoxicity: a potential approach? Food Chem Toxicol 112:342–354. CrossRefPubMedGoogle Scholar
  20. Lucioli J, Pinton P, Callu P, Laffitte J, Grosjean F, Kolf-Clauw M et al (2013) The food contaminant deoxynivalenol activates the mitogen activated protein kinases in the intestine: interest of ex vivo models as an alternative to in vivo experiments. Toxicon 66:31–36. CrossRefPubMedGoogle Scholar
  21. Maresca M (2013) From the gut to the brain: journey and pathophysiological effects of the food-associated mycotoxin deoxynivalenol. Toxins 5:784–820. CrossRefPubMedPubMedCentralGoogle Scholar
  22. Maresca M, Yahi N, Younes-Sakr L, Boyron M, Caporiccio B, Fantini J (2008) Both direct and indirect effects account for the pro-inflammatory activity of enteropathogenic mycotoxins on the human intestinal epithelium: stimulation of interleukin-8 secretion, potentiation of interleukin-1beta effect and increase in the transepithelial passage of commensal bacteria. Toxicol Appl Pharmacol 228:84–92. CrossRefPubMedGoogle Scholar
  23. Mayer E, Novak B, Springler A, Schwartz-Zimmermann HE, Nagl V, Reisinger N et al (2017) Effects of deoxynivalenol (DON) and its microbial biotransformation product deepoxy-deoxynivalenol (DOM-1) on a trout, pig, mouse, and human cell line. Mycotoxin Res 33:297–308. CrossRefPubMedPubMedCentralGoogle Scholar
  24. Meissonnier GM, Laffitte J, Raymond I, Benoit E, Cossalter AM, Pinton P et al (2008) Subclinical doses of T-2 toxin impair acquired immune response and liver cytochrome P450 in pigs. Toxicology 247:46–54. CrossRefPubMedGoogle Scholar
  25. Mikami O, Yamaguchi H, Murata H, Nakajima Y, Miyazaki S (2010) Induction of apoptotic lesions in liver and lymphoid tissues and modulation of cytokine mRNA expression by acute exposure to deoxynivalenol in piglets. J Vet Sci 11:107–113. CrossRefPubMedPubMedCentralGoogle Scholar
  26. Novak B, Vatzia E, Springler A, Pierron A, Gerner W, Reisinger N et al (2018) Bovine peripheral blood mononuclear cells are more sensitive to deoxynivalenol than those derived from poultry and swine. Toxins 10:152. CrossRefPubMedCentralGoogle Scholar
  27. Payros D, Alassane-Kpembi I, Pierron A, Loiseau N, Pinton P, Oswald IP (2016) Toxicology of deoxynivalenol and its acetylated and modified forms. Arch Toxicol 90:2931–2957. CrossRefPubMedGoogle Scholar
  28. Pestka JJ (2010a) Deoxynivalenol-induced proinflammatory gene expression: mechanisms and pathological sequelae. Toxins 2:1300–1317. CrossRefPubMedPubMedCentralGoogle Scholar
  29. Pestka JJ (2010b) Deoxynivalenol: mechanisms of action, human exposure, and toxicological relevance. Arch Toxicol 84:663–679. CrossRefPubMedGoogle Scholar
  30. Pestka JJ, Zhou HR, Moon Y, Chung YJ (2004) Cellular and molecular mechanisms for immune modulation by deoxynivalenol and other trichothecenes: unraveling a paradox. Toxicol Lett 153:61–73. CrossRefPubMedGoogle Scholar
  31. Pierron A, Mimoun S, Murate LS, Loiseau N, Lippi Y, Bracarense AP et al (2016a) Intestinal toxicity of the masked mycotoxin deoxynivalenol-3-beta-d-glucoside. Arch Toxicol 90:2037–2046. CrossRefPubMedGoogle Scholar
  32. Pierron A, Mimoun S, Murate LS, Loiseau N, Lippi Y, Bracarense AP et al (2016b) Microbial biotransformation of DON: molecular basis for reduced toxicity. Sci Rep 6:29105. CrossRefPubMedPubMedCentralGoogle Scholar
  33. Pinton P, Oswald IP (2014) Effect of deoxynivalenol and other type B trichothecenes on the intestine: a review. Toxins 6:1615–1643. CrossRefPubMedPubMedCentralGoogle Scholar
  34. Pinton P, Accensi F, Beauchamp E, Cossalter A-M, Callu P, Grosjean F et al (2008) Ingestion of deoxynivalenol (DON) contaminated feed alters the pig vaccinal immune responses. Toxicol Lett 177:215–222. CrossRefPubMedGoogle Scholar
  35. Pinton P, Tsybulskyy D, Lucioli J, Laffitte J, Callu P, Lyazhri F et al (2012) Toxicity of deoxynivalenol and its acetylated derivatives on the intestine: differential effects on morphology, barrier function, tight junction proteins, and mitogen-activated protein kinases. Toxicol Sci 130:180–190. CrossRefPubMedGoogle Scholar
  36. Schatzmayr G, Streit E (2013) Global occurrence of mycotoxins in the food and feed chain: facts and figures. World Mycotoxin J 6:213–222. CrossRefGoogle Scholar
  37. Schwartz-Zimmermann HE, Fruhmann P, Danicke S, Wiesenberger G, Caha S, Weber J et al (2015) Metabolism of deoxynivalenol and deepoxy-deoxynivalenol in broiler chickens, pullets, roosters and turkeys. Toxins 7:4706–4729. CrossRefPubMedPubMedCentralGoogle Scholar
  38. Shima J, Takase S, Takahashi Y, Iwai Y, Fujimoto H, Yamazaki M et al (1997) Novel detoxification of the trichothecene mycotoxin deoxynivalenol by a soil bacterium isolated by enrichment culture. Appl Environ Microbiol 63:3825–3830PubMedPubMedCentralGoogle Scholar
  39. Springler A, Hessenberger S, Reisinger N, Kern C, Nagl V, Schatzmayr G et al (2017) Deoxynivalenol and its metabolite deepoxy-deoxynivalenol: multi-parameter analysis for the evaluation of cytotoxicity and cellular effects. Mycotoxin Res 33:25–37. CrossRefPubMedGoogle Scholar
  40. Sundstol Eriksen G, Pettersson H, Lundh T (2004) Comparative cytotoxicity of deoxynivalenol, nivalenol, their acetylated derivatives and de-epoxy metabolites. Food Chem Toxicol 42:619–624. CrossRefPubMedGoogle Scholar
  41. Van De Walle J, During A, Piront N, Toussaint O, Schneider YJ, Larondelle Y (2010) Physio-pathological parameters affect the activation of inflammatory pathways by deoxynivalenol in Caco-2 cells. Toxicol in Vitro 24:1890–1898. CrossRefGoogle Scholar
  42. Wang Z, Wu Q, Kuca K, Dohnal V, Tian Z (2014) Deoxynivalenol: signaling pathways and human exposure risk assessment—an update. Arch Toxicol 88:1915–1928. CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Alix Pierron
    • 1
    • 2
  • Ana Paula F. L. Bracarense
    • 3
  • Anne-Marie Cossalter
    • 1
  • Joëlle Laffitte
    • 1
  • Heidi E. Schwartz-Zimmermann
    • 4
  • Gerd Schatzmayr
    • 2
  • Philippe Pinton
    • 1
  • Wulf-Dieter Moll
    • 2
  • Isabelle P. Oswald
    • 1
  1. 1.Toxalim (Research Center in Food Toxicology)Université de Toulouse, INRA, ENVT, INP-Purpan, UPSToulouse Cedex 3France
  2. 2.BIOMIN Research Center, Technopark 1TullnAustria
  3. 3.Universidade Estadual de Londrina, Lab. Patologia AnimalLondrinaBrazil
  4. 4.Center for Analytical Chemistry, Department of Agrobiotechnology (IFA-Tulln)University of Natural ressources and Life Sciences, Vienna (BOKU)TullnAustria

Personalised recommendations