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

Pierron, Alix; Bracarense, Ana Paula Frederico Rodrigues Loureiro; Cossalter, Anne‐Marie; Laffitte, Joëlle; Schwartz-Zimmermann, Heidi E.; Schatzmayr, Gerd; Pinton, Philippe; Moll, Wulf-Dieter; Oswald, Isabelle P.

doi:10.1007/s00204-018-2293-x

Cited by 31 publications

(23 citation statements)

References 42 publications

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“…In addition, our previous experiments with 16 μMDOM-1 did not reveal a loss of proliferation or the expression of co-stimulatory molecules in porcine T cells ( 5 ). However, more recently it was shown by in vivo experiments that DOM-1 can support cell proliferation in lymph nodes and antibody production to the model antigen ovalbumin to a similar extent as DON ( 47 ). Also, a study with bovine theca cells indicated that DOM-1 can increase mRNA expression of endoplasmatic reticulum stress-related proteins ( 48 ).…”

Section: Discussionmentioning

confidence: 99%

Deoxynivalenol Has the Capacity to Increase Transcription Factor Expression and Cytokine Production in Porcine T Cells

et al. 2020

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Deoxynivalenol (DON) is a Fusarium mycotoxin that frequently contaminates the feed of farm animals. Pigs with their monogastric digestive system are in particular sensitive to DON-contaminated feed. At high concentrations, DON causes acute toxic effects, whereas lower concentrations lead to more subtle changes in the metabolism. This applies in particular to the immune system, for which immunosuppressive but also immunostimulatory phenomena have been described. Research in human and rodent cell lines indicates that this may be partially explained by a binding of DON to the ribosome and subsequent influences on cell signaling molecules like mitogen-activated protein kinases. However, a detailed understanding of the influence of DON on functional traits of porcine immune cells is still lacking. In this study, we investigated the influence of DON on transcription factor expression and cytokine production within CD4 + , CD8 + , and γδ T cells in vitro. At a DON concentration, that already negatively affects proliferation after Concanavalin A stimulation (0.8 µM) an increase of T-bet expression in CD4 + and CD8 + T cells was observed. This increase in T-bet expression coincided with elevated levels of IFN-γ and TNF-α producing T-cell populations. Increases in T-bet expression and cytokine production were found in proliferating and non-proliferating T cells, although increases were more prominent in proliferating cell subsets. Differently, IL-17A production by CD4 + T cells was not influenced by DON. In addition, frequencies of regulatory T cells and their expression of Foxp3 were not affected. In γδ T cells, GATA-3 expression was slightly reduced by DON, whereas T-bet levels were only slightly modulated and hence IFN-γ, TNF-α, or IL-17A production were not affected. Our results show for the single-cell level that DON has the capacity to modulate the expression of transcription factors and related cytokines. In particular, they suggest that for CD4 + and CD8 + T cells, DON can drive T-cell differentiation into a pro-inflammatory type-1 direction, probably depending on the already prevailing cytokine milieu. This could have beneficial or detrimental effects in ongoing immune responses to infection or vaccination.

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Section: Discussionmentioning

confidence: 99%

Deoxynivalenol Has the Capacity to Increase Transcription Factor Expression and Cytokine Production in Porcine T Cells

et al. 2020

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“…With regard to histopathology, the PCNA level, and antibody response, DOM‐1 induced similar immune effects on DON in the pig model. Minimal intestinal toxicity and no hepatotoxicity were observed (Pierron et al., 2018).…”

Section: Toxicity Of Don and Its Modified Formsmentioning

confidence: 99%

Deoxynivalenol: Masked forms, fate during food processing, and potential biological remedies

Guo

Wang

et al. 2020

Comp Rev Food Sci Food Safe

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Deoxynivalenol (DON) has drawn global attention because of its prevalence and significant effects on human or animal health. Biological remedies for DON have been developed from preharvest to postharvest. Applying microbes, including bacteria, fungi (yeast and molds), and enzymes, results in inhibited synthesis, structural destruction, or adsorption of DON. DON can be degraded into masked forms by phase I metabolism or phase II metabolism. During food processing, DON content changes dynamically and is even transformed. Physical, chemical, thermal, or biological processes physically reduce DON content. Temperature, heating time, enzymes, food additives, microorganisms, food composition, contamination level, and other ingredients are key factors. Although DON content can be reduced during food processing, increases in other toxins, such as DON‐3‐β‐d‐glucoside and 3‐acetyl‐DON, can be potentially risky. The application of biodegradation methods in food processing bears research significance. Both microorganisms and enzymes can be potentially used. Novel techniques, such as RNA interference, omics technologies, or enzymes coupled with the genetic engineering method, can be introduced. This review systematically updates the understanding of masked forms of DON, biological degradation strategy, fate of DON during processing, and future trends for biodegradation. Challenges to the successful application of biological methods may include the stability and suitability of the detoxification agents, security of degradation products, and successful application for industrial production.

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“…Gerez et al (2015b) found that pigs given DON-contaminated feed (1.5, 2 and 3 mg/kg for 28 days) showed signi cant histological changes in the liver [50]. The study by Pierron et al (2018) found that piglets exposed by gavage to 1 and 0.5 nM DON/kg b.w/day for 3 weeks revealed a slight decrease in weight gain [51]. A diet containing 8 mg/kg DON fed for 4 weeks disrupted the immune-related processes in the liver of piglets [52].…”

Section: Donmentioning

confidence: 99%

Dietary exposure of deoxynivalenol affected cytochrome P450 and growth related-gene expression via DNA methylation in piglet liver

Liu

Zhu

et al. 2020

Preprint

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Background Deoxynivalenol (DON) is an inevitable contaminant in animal feed and human food and can lead to decreased appetite and growth retardation in children and piglets, which are often used as models for children. Hepatotoxicity induced by DON is closely related to growth inhibition. Although many molecular mechanisms are related to the liver damage caused by DON, few studies have been done on cytochrome P450 (CYP450s) and DNA methylation, and the role of DNA methylation in growth inhibition of piglets was also unclear. Results In the present study, piglets were randomly assigned to the following three different dietary treatments for 4 weeks: control diet, diet containing 1 mg DON/kg feed, and diet containing 3 mg DON/kg feed. Compared to the control group, elevated alanine aminotransferase activity and globulin level were observed in DON groups; however, aspartate aminotransferase activity was decreased in 3 mg/kg DON group. DON exposure increased the mRNA expression of CYP450s including CYP1A1, CYP1A2, CYP2B22, CYP2C33, CYP2D25, CYP2E1, CYP3A22 and CYP3A39, in which DNA methylation was involved in the regulation of the expression of these enzymes. By estimating the benchmark dose value of the metabolic enzymes, CYP1A1 was found to be the most sensitive metabolic enzyme to evaluate the clinical liver injury caused by DON. DON upregulated the expression of DNA methyltransferases (DNMT1 and DNMT3B) in a dose-dependent manner, thus increasing the level of 5-mC in the whole genome. Notably, DON downregulated the expression of nicotinamide n-methyltransferase, possibly reducing the weight of the piglets. Additionally, 1 mg/kg DON decreased the expression of galanin-like peptide (GALP), while 3 mg/kg DON significantly increased the level of GALP through DNA methylation, thus affecting the appetite of the piglets. DON can significantly reduce the methylation level of insulin-like growth factor 1 (IGF-1) promoter and thus increase its expression. Conclusions Taken together, increased CYP450 expression and DNA methylation are important mechanisms of liver injury and growth inhibition induced by DON, which provide future reference values determination of antagonistic toxicity.

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

Cited by 31 publications

References 42 publications

Deoxynivalenol Has the Capacity to Increase Transcription Factor Expression and Cytokine Production in Porcine T Cells

Deoxynivalenol Has the Capacity to Increase Transcription Factor Expression and Cytokine Production in Porcine T Cells

Deoxynivalenol: Masked forms, fate during food processing, and potential biological remedies

Dietary exposure of deoxynivalenol affected cytochrome P450 and growth related-gene expression via DNA methylation in piglet liver

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