Intestinal toxicity of the type B trichothecene mycotoxin fusarenon-X: whole transcriptome profiling reveals new signaling pathways

Alassane-Kpémbi, Imourana; Gerez, Juliana Rubira; Cossalter, Anne‐Marie; Neves, Manon; Laffitte, Joëlle; Naylies, Claire; Lippi, Yannick; Kolf‐Clauw, Martine; Bracarense, Ana Paula Loureiro; Pinton, Philippe; Oswald, Isabelle P.

doi:10.1038/s41598-017-07155-2

Cited by 31 publications

(32 citation statements)

References 63 publications

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“…FUS‐X is mainly found in cereals, and co‐occurs with DON and NIV, however in lower levels (Perkowski, Stachowiak, Kiecana, Goliñski, & Chelkowski, ; Tolosa et al., ). The toxicity of FUS‐X, however, has been found to be more potent than other type B‐trichothecenes (Alassane‐Kpembi et al., ). FUS‐X mainly affects organs that have actively dividing cells such as hematopoietic tissues, spleen, and the thymus, and exerts intestinal inflammation, inhibits protein synthesis, induces apoptosis, and alters genetic material causing cell cycle delays, chromosomal aberrations, and sister chromatid exchanges (IARC, ).…”

Section: Fusarenon‐xmentioning

confidence: 99%

Mycotoxin Biomarkers of Exposure: A Comprehensive Review

Vidal

Mengelers

Yang³

et al. 2018

Comp Rev Food Sci Food Safe

154

137

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To date, the use of biomarkers has become generally accepted. Biomarker-driven research has been proposed as a successful method to assess the exposure to xenobiotics by using concentrations of the parent compounds and/or metabolites in biological matrices such as urine or blood. However, the identification and validation of biomarkers of exposure remain a challenge. Recent advances in high-resolution mass spectrometry along with new analytical (postacquisition data-mining) techniques will improve the quality and output of the biomarker identification process. Chronic or even acute exposure to mycotoxins remains a daily fact, and therefore it is crucial that the mycotoxins' metabolism is unravelled so more knowledge on biomarkers in humans and animals is acquired. This review aims to provide the scientific community with a comprehensive overview of reported in vitro and in vivo mycotoxin metabolism studies in relation to biomarkers of exposure for deoxynivalenol, nivalenol, fusarenon-X, T-2 toxin, diacetoxyscirpenol, ochratoxin A, citrinin, fumonisins, zearalenone, aflatoxins, and sterigmatocystin.

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Section: Fusarenon‐xmentioning

confidence: 99%

Mycotoxin Biomarkers of Exposure: A Comprehensive Review

Vidal

Mengelers

Yang³

et al. 2018

Comp Rev Food Sci Food Safe

154

137

View full text Add to dashboard Cite

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“…Inflammation is a hallmark of the toxicity of DON and FX on epithelial intestinal cells [ 24 ]. To address whether mycotoxins induced pro-inflammatory responses by airway cells, we measured the concentrations of IL-6 and IL-8 in culture supernatants of cells exposed for 24 h (16HBE14o-, hAECN and hAECB cells) or 48 h (A549 cells) to medium or DON, NIV and FX used alone or in combination at f a 0.1, 0.3 and 0.5 ( Figure 4 ).…”

Section: Resultsmentioning

confidence: 99%

“…In vitro experiments are however crucial to address the mode of action of mycotoxins with similar molecular structures and define their interactions when used in combination. This information should be taken into account when analysing the hazard of occupational exposure to mycotoxins by inhalation and its impact on airway cells, which, as suggested [ 23 , 24 ], cannot be deduced from experiments evaluating single mycotoxins.…”

Section: Discussionmentioning

confidence: 99%

“…Yet increasing amounts of evidence suggest that this may not be the case. Indeed, while DON, NIV and FX bind eukaryotic ribosomes and inhibit protein synthesis [ 20 ] and modulate cytokine expression [ 20 , 21 , 22 ], the toxicity of DON on intestinal cells significantly deviates from that of NIV [ 23 ] and FX [ 24 , 25 , 26 , 27 ]. Dissimilarities of action of DON, NIV and FX might also occur in lung tissues.…”

Section: Introductionmentioning

confidence: 99%

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Primary and Immortalized Human Respiratory Cells Display Different Patterns of Cytotoxicity and Cytokine Release upon Exposure to Deoxynivalenol, Nivalenol and Fusarenon-X

Lopes

Vacher

Ciarlo

et al. 2017

Toxins

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The type B trichothecene mycotoxins deoxynivalenol (DON), nivalenol (NIV) and fusarenon-X (FX) are structurally related secondary metabolites frequently produced by Fusarium on wheat. Consequently, DON, NIV and FX contaminate wheat dusts, exposing grain workers to toxins by inhalation. Those trichothecenes at low, relevant, exposition concentrations have differential effects on intestinal cells, but whether such differences exist with respiratory cells is mostly unknown, while it is required to assess the combined risk of exposure to mycotoxins. The goal of the present study was to compare the effects of DON, NIV and FX alone or in combination on the viability and IL-6 and IL-8-inducing capacity of human epithelial cells representative of the respiratory tract: primary human airway epithelial cells of nasal (hAECN) and bronchial (hAECB) origin, and immortalized human bronchial (16HBE14o-) and alveolar (A549) epithelial cell lines. We report that A549 cells are particularly resistant to the cytotoxic effects of mycotoxins. FX is more toxic than DON and NIV for all epithelial cell types. Nasal and bronchial primary cells are more sensitive than bronchial and alveolar cell lines to combined mycotoxin mixtures at low concentrations, although they are less sensitive to mycotoxins alone. Interactions between mycotoxins at low concentrations are rarely additive and are observed only for DON/NIV and NIV/FX on hAECB cells and DON/NIV/FX on A549 cells. Most interactions at low mycotoxin concentrations are synergistic, antagonistic interactions being observed only for DON/FX on hAECB, DON/NIV on 16HBE14o- and NIV/FX on A549 cells. DON, NIV and FX induce, albeit at different levels, IL-6 and IL-8 release by all cell types. However, NIV and FX at concentrations of low cytotoxicity induce IL-6 release by hAECB and A549 cells, and IL-8 release by hAECN cells. Overall, these data suggest that combined exposure to mycotoxins at low concentrations have a stronger effect on primary nasal epithelial cells than on bronchial epithelial cells and activate different inflammatory pathways. This information is particularly relevant for future studies about the hazard of occupational exposure to mycotoxins by inhalation and its impact on the respiratory tract.

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“…They promote each other’s expression and cooperate to activate the expressions of thousands of genes involved in late adipogenesis [ 14 ]. A recent study reported that another type B trichothecene, fusarenon-X, is a stronger inducer of intestinal inflammation, and PPARγ is also downregulated after its administration [ 46 ]. In HCT-8 cells, DON may suppress PPARγ expression via CCAAT/enhancer-binding protein homologous protein (CHOP).…”

Section: Discussionmentioning

confidence: 99%

Deoxynivalenol Exposure Suppresses Adipogenesis by Inhibiting the Expression of Peroxisome Proliferator-Activated Receptor Gamma 2 (PPARγ2) in 3T3-L1 Cells

Zhao

Tang

Lin

et al. 2020

IJMS

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Deoxynivalenol (DON)—a type B trichothecene mycotoxin, mainly produced by the secondary metabolism of Fusarium—has toxic effects on animals and humans. Although DON’s toxicity in many organs including the adrenal glands, thymus, stomach, spleen, and colon has been addressed, its effects on adipocytes have not been investigated. In this study, 3T3-L1 cells were chosen as the cell model and treated with less toxic doses of DON (100 ng/mL) for 7 days. An inhibition of adipogenesis and decrease in triglycerides (TGs) were observed. DON exposure significantly downregulated the expression of PPARγ2 and C/EBPα, along with that of other adipogenic marker genes in 3T3-L1 cells and BALB/c mice. The anti-adipogenesis effect of DON and the downregulation of the expression of adipogenic marker genes were effectively reversed by PPARγ2 overexpression. The repression of PPARγ2′s expression is the pivotal event during DON exposure regarding adipogenesis. DON exposure specifically decreased the di-/trimethylation levels of Histone 3 at lysine 4 in 3T3-L1 cells, therefore weakening the enrichment of H3K4me2 and H3K4me3 at the Pparγ2 promoter and suppressing its expression. Conclusively, DON exposure inhibited PPARγ2 expression via decreasing H3K4 methylation, downregulated the expression of PPARγ2-regulated adipogenic marker genes, and consequently suppressed the intermediate and late stages of adipogenesis. Our results broaden the current understanding of DON’s toxic effects and provide a reference for addressing the toxicological mechanism of DON’s interference with lipid homeostasis.

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Intestinal toxicity of the type B trichothecene mycotoxin fusarenon-X: whole transcriptome profiling reveals new signaling pathways

Cited by 31 publications

References 63 publications

Mycotoxin Biomarkers of Exposure: A Comprehensive Review

Mycotoxin Biomarkers of Exposure: A Comprehensive Review

Primary and Immortalized Human Respiratory Cells Display Different Patterns of Cytotoxicity and Cytokine Release upon Exposure to Deoxynivalenol, Nivalenol and Fusarenon-X

Deoxynivalenol Exposure Suppresses Adipogenesis by Inhibiting the Expression of Peroxisome Proliferator-Activated Receptor Gamma 2 (PPARγ2) in 3T3-L1 Cells

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