Abstract
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.
Similar content being viewed by others
References
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. https://doi.org/10.1096/fj.13-238717
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. https://doi.org/10.1038/s41598-017-07155-2
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. https://doi.org/10.1007/s00204-016-1902-9
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. https://doi.org/10.1371/journal.pone.0100907
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. https://doi.org/10.1017/S0007114511004946
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. https://doi.org/10.3390/toxins9100334
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. https://doi.org/10.1051/vetres/2009023
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. https://doi.org/10.2903/j.efsa.2017.4718
Gerez JR, Desto SS, Bracarense A (2016) Deoxynivalenol induces toxic effects in the ovaries of pigs: an ex vivo approach. Theriogenology 90:94–100. https://doi.org/10.1016/j.theriogenology.2016.10.023
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. https://doi.org/10.3382/ps.2011-01741
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. https://doi.org/10.1002/jat.3083
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. https://doi.org/10.1016/j.fct.2010.07.040
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. https://doi.org/10.1016/j.bcp.2012.02.007
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. https://doi.org/10.1021/jf400213q
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. https://doi.org/10.1093/biolre/iox127
Helke KL, Swindle MM (2013) Animal models of toxicology testing: the role of pigs. Expert Opin Drug Metab Toxicol 9:127–139. https://doi.org/10.1517/17425255.2013.739607
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. https://doi.org/10.1007/s00253-011-3401-5
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. https://doi.org/10.1080/19440049.2011.576402
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. https://doi.org/10.1016/j.fct.2018.01.013
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. https://doi.org/10.1016/j.toxicon.2013.01.024
Maresca M (2013) From the gut to the brain: journey and pathophysiological effects of the food-associated mycotoxin deoxynivalenol. Toxins 5:784–820. https://doi.org/10.3390/toxins5040784
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. https://doi.org/10.1016/j.taap.2007.11.013
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. https://doi.org/10.1007/s12550-017-0289-7
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. https://doi.org/10.1016/j.tox.2008.02.003
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. https://doi.org/10.4142/jvs.2010.11.2.107
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. https://doi.org/10.3390/toxins10040152
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. https://doi.org/10.1007/s00204-016-1826-4
Pestka JJ (2010a) Deoxynivalenol-induced proinflammatory gene expression: mechanisms and pathological sequelae. Toxins 2:1300–1317. https://doi.org/10.3390/toxins2061300
Pestka JJ (2010b) Deoxynivalenol: mechanisms of action, human exposure, and toxicological relevance. Arch Toxicol 84:663–679. https://doi.org/10.1007/s00204-010-0579-8
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. https://doi.org/10.1016/j.toxlet.2004.04.023
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. https://doi.org/10.1007/s00204-015-1592-8
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. https://doi.org/10.1038/srep29105
Pinton P, Oswald IP (2014) Effect of deoxynivalenol and other type B trichothecenes on the intestine: a review. Toxins 6:1615–1643. https://doi.org/10.3390/toxins6051615
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. https://doi.org/10.1016/jtoxlet.2008.01.015
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. https://doi.org/10.1093/toxsci/kfs239
Schatzmayr G, Streit E (2013) Global occurrence of mycotoxins in the food and feed chain: facts and figures. World Mycotoxin J 6:213–222. https://doi.org/10.3920/WMJ2013.1572
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. https://doi.org/10.3390/toxins7114706
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 63:3825–3830
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. https://doi.org/10.1007/s12550-016-0260-z
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. https://doi.org/10.1016/j.fct.2003.11.006
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. https://doi.org/10.1016/j.tiv.2010.07.008
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. https://doi.org/10.1007/s00204-014-1354-z
Acknowledgements
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.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare no conflicts of interest during experimental work reported here.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Supplementary material 2 (MP4 146153 KB)
Rights and permissions
About this article
Cite this article
Pierron, A., Bracarense, A.P.F.L., Cossalter, AM. et al. Deepoxy-deoxynivalenol retains some immune-modulatory properties of the parent molecule deoxynivalenol in piglets. Arch Toxicol 92, 3381–3389 (2018). https://doi.org/10.1007/s00204-018-2293-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00204-018-2293-x