Project description:To investigate the possible toxics effects of newly discovered mycotoxins NX and 3ANX and compare with the known effects of DON, we performed a microarray to study their effects on expression profile of intestinal explants
Project description:Deoxynivalenol (DON) is a frequent mycotoxin in grains, produced by Fusarium fungi, which demonstre multiple side effects such as modulation of immune responses, reduced feed intake and weight gain or impairment of the intestinal barrier function. Among animal species, pigs are the best model for humans and are very sensitive to DON. In wheat, DON can be conjugated to glucose to form DON-3-β-D-glucoside (D3G). Some bacteria isolated from digestive tracts or soil, are also able to de-epoxydize or epimerize DON to metabolites such as deepoxy-deoxynivalenol (DOM-1) or 3-epi-deoxynivalenol (epi-DON). The toxicity of these DON metabolites is poorly documented. By the way of ingestion, the intestine is the first organ exposed to these molecules and so constitute a relevant model. The aim of this study was to compare the intestinal toxicity of three DON metabolites (D3G, DOM-1 and epi-DON) with the one of DON. Intestinal explants from 6 pigs were treated with 10mM DON, D3G, DOM-1 or epi-DON for 4 hours and transcriptomic analysis was performed using an âAgilent Porcinet 60Kâ. Jejunal explants from 4 piglets aged of 5 weeks were sampled and exposed in vitro to differents molecules (DON, D3G, DOM-1 & 3-epi-DON) at 10µM during 4h. Then RNA was extracted.
Project description:Deoxynivalenol (DON) is a frequent mycotoxin in grains, produced by Fusarium fungi, which demonstre multiple side effects such as modulation of immune responses, reduced feed intake and weight gain or impairment of the intestinal barrier function. Among animal species, pigs are the best model for humans and are very sensitive to DON. In wheat, DON can be conjugated to glucose to form DON-3-β-D-glucoside (D3G). Some bacteria isolated from digestive tracts or soil, are also able to de-epoxydize or epimerize DON to metabolites such as deepoxy-deoxynivalenol (DOM-1) or 3-epi-deoxynivalenol (epi-DON). The toxicity of these DON metabolites is poorly documented. By the way of ingestion, the intestine is the first organ exposed to these molecules and so constitute a relevant model. The aim of this study was to compare the intestinal toxicity of three DON metabolites (D3G, DOM-1 and epi-DON) with the one of DON. Intestinal explants from 6 pigs were treated with 10mM DON, D3G, DOM-1 or epi-DON for 4 hours and transcriptomic analysis was performed using an “Agilent Porcinet 60K”.
Project description:NX is a type A trichothecene produced by Fusarium graminearum with limited information on its toxicity. NX is structurally similar to deoxynivalenol (DON), only differing by the lacking keto group at C8. Because of the structural similarity of the two toxins as well as their potential co-occurrence in food and feed, it is of interest to determine the toxicity of this new compound. In this study, we compared the protein composition of the extracellular media of pig intestinal explants (secretome) exposed to 10 µM of DON or NX for 4 h compared with controls. The combination of two complementary quantitative proteomic approaches (a gel-based and a gel-free approach) identified 18 and 23 differentially abundant proteins (DAPs) for DON and NX, respectively, compared to controls. Functional analysis suggested that, whereas DON toxicity was associated with decreased cell viability and cell destruction, NX toxicity was associated with an enrichment of mitochondrial proteins in the secretome. The presence of these proteins may be associated with the already known ability of NX to induce an intestinal inflammation. Overall, our results indicated that DON- and NX-induced changes in the extracellular proteome of intestinal explants are different. The increased leakage/secretion of mitochondrial proteins by NX may be a feature of NX toxicity.
Project description:Deoxynivalenol (DON) is a fungal toxin mainly produced by Fusarium graminearum and Fusarium graminearum, and is present in cereal crops such as wheat, barley, oats, rye, and corn. It is widely polluted worldwide. DON and its related derivatives have a wide range of toxic effects on humans and animals. This study used zebrafish models and different cell models to verify the toxic effects of DON, and explored the mechanism of DON mediated Jurkat apoptosis and inhibition of M2 macrophage differentiation. The results indicate that the toxic effects of these fungal toxins differ significantly among various cell types. For Jurkat T cells, the IC50 values of DON, NIV, 15 Ac DON, and 3-Ac DON were 488.6 nM, 318.2 nM, 544 nM, and 6516 nM, respectively. There are significant differences in the effects on M2 polarization of macrophages, and DON, NIV, and 15 Ac DON can inhibit M2 differentiation and function of macrophages at lower dose levels. Indicating that immune toxicity is an important toxic effect of DON and its related substances. Research on its mechanism has shown that DON can target protein processing processes, interfere with the normal synthesis and folding of proteins in cells, and trigger cellular stress responses. These findings reveal the toxic effects and potential mechanisms of DON on human immune cells, providing a scientific basis for preventing and controlling DON pollution and its harm to human health.
Project description:Deoxynivalenol (DON) is a fungal toxin mainly produced by Fusarium graminearum and Fusarium graminearum, and is present in cereal crops such as wheat, barley, oats, rye, and corn. It is widely polluted worldwide. DON and its related derivatives have a wide range of toxic effects on humans and animals. This study used zebrafish models and different cell models to verify the toxic effects of DON, and explored the mechanism of DON mediated Jurkat apoptosis and inhibition of M2 macrophage differentiation. The results indicate that the toxic effects of these fungal toxins differ significantly among various cell types. For Jurkat T cells, the IC50 values of DON, NIV, 15 Ac DON, and 3-Ac DON were 488.6 nM, 318.2 nM, 544 nM, and 6516 nM, respectively. There are significant differences in the effects on M2 polarization of macrophages, and DON, NIV, and 15 Ac DON can inhibit M2 differentiation and function of macrophages at lower dose levels. Indicating that immune toxicity is an important toxic effect of DON and its related substances. Research on its mechanism has shown that DON can target protein processing processes, interfere with the normal synthesis and folding of proteins in cells, and trigger cellular stress responses. These findings reveal the toxic effects and potential mechanisms of DON on human immune cells, providing a scientific basis for preventing and controlling DON pollution and its harm to human health.
Project description:Deoxynivalenol (DON) is a fungal toxin mainly produced by Fusarium graminearum and Fusarium graminearum, and is present in cereal crops such as wheat, barley, oats, rye, and corn. It is widely polluted worldwide. DON and its related derivatives have a wide range of toxic effects on humans and animals. This study used zebrafish models and different cell models to verify the toxic effects of DON, and explored the mechanism of DON mediated Jurkat apoptosis and inhibition of M2 macrophage differentiation. The results indicate that the toxic effects of these fungal toxins differ significantly among various cell types. For Jurkat T cells, the IC50 values of DON, NIV, 15 Ac DON, and 3-Ac DON were 488.6 nM, 318.2 nM, 544 nM, and 6516 nM, respectively. There are significant differences in the effects on M2 polarization of macrophages, and DON, NIV, and 15 Ac DON can inhibit M2 differentiation and function of macrophages at lower dose levels. Indicating that immune toxicity is an important toxic effect of DON and its related substances. Research on its mechanism has shown that DON can target protein processing processes, interfere with the normal synthesis and folding of proteins in cells, and trigger cellular stress responses. These findings reveal the toxic effects and potential mechanisms of DON on human immune cells, providing a scientific basis for preventing and controlling DON pollution and its harm to human health.
Project description:Transcriptional profiling of log and stationary phase S. Typhimurium, comparing untreated controls with Deoxynivalenol treated samples. Each array used labelled cDNA against a common genomic DNA reference. Triplicate arrays were carried out for each of the 4 conditions: untreated log phase, untreated stationary phase, DON treated log phase and DON treated stationary phase