Intestinal toxicity of the type B trichothecene mycotoxin fusarenon-X: whole transcriptome profiling reveals new signaling pathways
Abstract The few data available on fusarenon-X (FX) do not support the derivation of health-based guidance values, although preliminary results suggest higher toxicity than other regulated trichothecenes. Using histo-morphological analysis and whole transcriptome profiling, this study was designed t...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2017-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-07155-2 |
| _version_ | 1818840984598872064 |
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| author | Imourana Alassane-Kpembi Juliana Rubira Gerez Anne-Marie Cossalter Manon Neves Joëlle Laffitte Claire Naylies Yannick Lippi Martine Kolf-Clauw Ana Paula L. Bracarense Philippe Pinton Isabelle P. Oswald |
| author_facet | Imourana Alassane-Kpembi Juliana Rubira Gerez Anne-Marie Cossalter Manon Neves Joëlle Laffitte Claire Naylies Yannick Lippi Martine Kolf-Clauw Ana Paula L. Bracarense Philippe Pinton Isabelle P. Oswald |
| author_sort | Imourana Alassane-Kpembi |
| collection | DOAJ |
| description | Abstract The few data available on fusarenon-X (FX) do not support the derivation of health-based guidance values, although preliminary results suggest higher toxicity than other regulated trichothecenes. Using histo-morphological analysis and whole transcriptome profiling, this study was designed to obtain a global view of the intestinal alterations induced by FX. Deoxynivalenol (DON) served as a benchmark. FX induced more severe histological alterations than DON. Inflammation was the hallmark of the molecular toxicity of both mycotoxins. The benchmark doses for the up-regulation of key inflammatory genes by FX were 4- to 45-fold higher than the previously reported values for DON. The transcriptome analysis revealed that both mycotoxins down-regulated the peroxisome proliferator-activated receptor (PPAR) and liver X receptor - retinoid X receptor (LXR-RXR) signaling pathways that control lipid metabolism. Interestingly, several pathways, including VDR/RXR activation, ephrin receptor signaling, and GNRH signaling, were specific to FX and thus discriminated the transcriptomic fingerprints of the two mycotoxins. These results demonstrate that FX induces more potent intestinal inflammation than DON. Moreover, although the mechanisms of toxicity of both mycotoxins are similar in many ways, this study emphasize specific pathways targeted by each mycotoxin, highlighting the need for specific mechanism-based risk assessments of Fusarium mycotoxins. |
| first_indexed | 2024-12-19T04:18:52Z |
| format | Article |
| id | doaj.art-7af54e295d7844b0bdaef1cb9f145286 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-19T04:18:52Z |
| publishDate | 2017-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-7af54e295d7844b0bdaef1cb9f1452862022-12-21T20:36:14ZengNature PortfolioScientific Reports2045-23222017-08-017111410.1038/s41598-017-07155-2Intestinal toxicity of the type B trichothecene mycotoxin fusarenon-X: whole transcriptome profiling reveals new signaling pathwaysImourana Alassane-Kpembi0Juliana Rubira Gerez1Anne-Marie Cossalter2Manon Neves3Joëlle Laffitte4Claire Naylies5Yannick Lippi6Martine Kolf-Clauw7Ana Paula L. Bracarense8Philippe Pinton9Isabelle P. Oswald10Toxalim, Research Center in Food Toxicology, Université de Toulouse, INRA, ENVT, INP- PURPAN, UPSToxalim, Research Center in Food Toxicology, Université de Toulouse, INRA, ENVT, INP- PURPAN, UPSToxalim, Research Center in Food Toxicology, Université de Toulouse, INRA, ENVT, INP- PURPAN, UPSToxalim, Research Center in Food Toxicology, Université de Toulouse, INRA, ENVT, INP- PURPAN, UPSToxalim, Research Center in Food Toxicology, Université de Toulouse, INRA, ENVT, INP- PURPAN, UPSToxalim, Research Center in Food Toxicology, Université de Toulouse, INRA, ENVT, INP- PURPAN, UPSToxalim, Research Center in Food Toxicology, Université de Toulouse, INRA, ENVT, INP- PURPAN, UPSToxalim, Research Center in Food Toxicology, Université de Toulouse, INRA, ENVT, INP- PURPAN, UPSLaboratory of Animal Pathology, Department of Veterinary Preventive Medicine, Universidade Estadual de LondrinaToxalim, Research Center in Food Toxicology, Université de Toulouse, INRA, ENVT, INP- PURPAN, UPSToxalim, Research Center in Food Toxicology, Université de Toulouse, INRA, ENVT, INP- PURPAN, UPSAbstract The few data available on fusarenon-X (FX) do not support the derivation of health-based guidance values, although preliminary results suggest higher toxicity than other regulated trichothecenes. Using histo-morphological analysis and whole transcriptome profiling, this study was designed to obtain a global view of the intestinal alterations induced by FX. Deoxynivalenol (DON) served as a benchmark. FX induced more severe histological alterations than DON. Inflammation was the hallmark of the molecular toxicity of both mycotoxins. The benchmark doses for the up-regulation of key inflammatory genes by FX were 4- to 45-fold higher than the previously reported values for DON. The transcriptome analysis revealed that both mycotoxins down-regulated the peroxisome proliferator-activated receptor (PPAR) and liver X receptor - retinoid X receptor (LXR-RXR) signaling pathways that control lipid metabolism. Interestingly, several pathways, including VDR/RXR activation, ephrin receptor signaling, and GNRH signaling, were specific to FX and thus discriminated the transcriptomic fingerprints of the two mycotoxins. These results demonstrate that FX induces more potent intestinal inflammation than DON. Moreover, although the mechanisms of toxicity of both mycotoxins are similar in many ways, this study emphasize specific pathways targeted by each mycotoxin, highlighting the need for specific mechanism-based risk assessments of Fusarium mycotoxins.https://doi.org/10.1038/s41598-017-07155-2 |
| spellingShingle | Imourana Alassane-Kpembi Juliana Rubira Gerez Anne-Marie Cossalter Manon Neves Joëlle Laffitte Claire Naylies Yannick Lippi Martine Kolf-Clauw Ana Paula L. Bracarense Philippe Pinton Isabelle P. Oswald Intestinal toxicity of the type B trichothecene mycotoxin fusarenon-X: whole transcriptome profiling reveals new signaling pathways Scientific Reports |
| title | Intestinal toxicity of the type B trichothecene mycotoxin fusarenon-X: whole transcriptome profiling reveals new signaling pathways |
| title_full | Intestinal toxicity of the type B trichothecene mycotoxin fusarenon-X: whole transcriptome profiling reveals new signaling pathways |
| title_fullStr | Intestinal toxicity of the type B trichothecene mycotoxin fusarenon-X: whole transcriptome profiling reveals new signaling pathways |
| title_full_unstemmed | Intestinal toxicity of the type B trichothecene mycotoxin fusarenon-X: whole transcriptome profiling reveals new signaling pathways |
| title_short | Intestinal toxicity of the type B trichothecene mycotoxin fusarenon-X: whole transcriptome profiling reveals new signaling pathways |
| title_sort | intestinal toxicity of the type b trichothecene mycotoxin fusarenon x whole transcriptome profiling reveals new signaling pathways |
| url | https://doi.org/10.1038/s41598-017-07155-2 |
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