Metabolomics and Lipidomics Reveal the Metabolic Disorders Induced by Single and Combined Exposure of Fusarium Mycotoxins in IEC-6 Cells
Deoxynivalenol (DON), fumonisin B<sub>1</sub> (FB<sub>1</sub>), and zearalenone (ZEN) are typical fusarium mycotoxins that occur worldwide in foodstuffs, posing significant health hazards to humans and animals. Single and combined exposure of DON, FB<sub>1</sub>,...
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2025-01-01
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| author | Xinlu Wang Yanyang Xu Haiqi Yu Yushun Lu Yongzhong Qian Meng Wang |
| author_facet | Xinlu Wang Yanyang Xu Haiqi Yu Yushun Lu Yongzhong Qian Meng Wang |
| author_sort | Xinlu Wang |
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| description | Deoxynivalenol (DON), fumonisin B<sub>1</sub> (FB<sub>1</sub>), and zearalenone (ZEN) are typical fusarium mycotoxins that occur worldwide in foodstuffs, posing significant health hazards to humans and animals. Single and combined exposure of DON, FB<sub>1</sub>, and ZEN leads to intestinal toxicity but the toxicology mechanism research is still limited. In this study, we explored the cytotoxicity effects of DON, FB<sub>1</sub>, ZEN, and their combination in rat intestinal epithelial cell line 6 (IEC-6) cells. Cell viability results showed that the cytotoxicity potency ranking was DON > ZEN > FB<sub>1</sub>. Furthermore, both DON + FB<sub>1</sub> and DON + ZEN presented synergism to antagonism effects based on a combination index (CI)-isobologram equation model. Integrated metabolomics and lipidomics was adopted to explore cell metabolism disorders induced by fusarium mycotoxin exposure. A total of 2011 metabolites and 670 lipids were identified. An overlap of 37 and 62 differential compounds was confirmed after single and combined mycotoxin exposure by multivariate analysis, respectively. Some of the differential compounds were endocellular antioxidants and were significantly downregulated in mycotoxin exposure groups, indicating metabolic disorders as well as antioxidant capacity damage in cells. Pathway enrichment analysis annotated ethanol metabolism production of ROS by CYP2E1 was mainly involved in the disturbance of DON, FB<sub>1</sub>, and ZEN. The results obtained in this study help to define the toxicity effects of DON, FB<sub>1</sub>, and ZEN singly and in co-existence, providing an important scientific basis for combined risk recognition of mycotoxin contamination. |
| format | Article |
| id | doaj-art-1c8b395809a5419c92010818c01a25c9 |
| institution | Kabale University |
| issn | 2304-8158 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Foods |
| spelling | doaj-art-1c8b395809a5419c92010818c01a25c92025-01-24T13:32:57ZengMDPI AGFoods2304-81582025-01-0114223010.3390/foods14020230Metabolomics and Lipidomics Reveal the Metabolic Disorders Induced by Single and Combined Exposure of Fusarium Mycotoxins in IEC-6 CellsXinlu Wang0Yanyang Xu1Haiqi Yu2Yushun Lu3Yongzhong Qian4Meng Wang5Institute of Quality Standard and Testing Technology, Beijing Academy of Agriculture and Forestry Sciences, Beijing 100097, ChinaInstitute of Quality Standards and Testing Technology for Agro-Products, Chinese Academy of Agricultural Sciences, Key Laboratory of Agri-Food Quality and Safety, Ministry of Agriculture and Rural Affairs, Beijing 100081, ChinaInstitute of Quality Standard and Testing Technology, Beijing Academy of Agriculture and Forestry Sciences, Beijing 100097, ChinaInstitute of Quality Standards and Testing Technology for Agro-Products, Chinese Academy of Agricultural Sciences, Key Laboratory of Agri-Food Quality and Safety, Ministry of Agriculture and Rural Affairs, Beijing 100081, ChinaInstitute of Quality Standards and Testing Technology for Agro-Products, Chinese Academy of Agricultural Sciences, Key Laboratory of Agri-Food Quality and Safety, Ministry of Agriculture and Rural Affairs, Beijing 100081, ChinaInstitute of Quality Standard and Testing Technology, Beijing Academy of Agriculture and Forestry Sciences, Beijing 100097, ChinaDeoxynivalenol (DON), fumonisin B<sub>1</sub> (FB<sub>1</sub>), and zearalenone (ZEN) are typical fusarium mycotoxins that occur worldwide in foodstuffs, posing significant health hazards to humans and animals. Single and combined exposure of DON, FB<sub>1</sub>, and ZEN leads to intestinal toxicity but the toxicology mechanism research is still limited. In this study, we explored the cytotoxicity effects of DON, FB<sub>1</sub>, ZEN, and their combination in rat intestinal epithelial cell line 6 (IEC-6) cells. Cell viability results showed that the cytotoxicity potency ranking was DON > ZEN > FB<sub>1</sub>. Furthermore, both DON + FB<sub>1</sub> and DON + ZEN presented synergism to antagonism effects based on a combination index (CI)-isobologram equation model. Integrated metabolomics and lipidomics was adopted to explore cell metabolism disorders induced by fusarium mycotoxin exposure. A total of 2011 metabolites and 670 lipids were identified. An overlap of 37 and 62 differential compounds was confirmed after single and combined mycotoxin exposure by multivariate analysis, respectively. Some of the differential compounds were endocellular antioxidants and were significantly downregulated in mycotoxin exposure groups, indicating metabolic disorders as well as antioxidant capacity damage in cells. Pathway enrichment analysis annotated ethanol metabolism production of ROS by CYP2E1 was mainly involved in the disturbance of DON, FB<sub>1</sub>, and ZEN. The results obtained in this study help to define the toxicity effects of DON, FB<sub>1</sub>, and ZEN singly and in co-existence, providing an important scientific basis for combined risk recognition of mycotoxin contamination.https://www.mdpi.com/2304-8158/14/2/230fusarium mycotoxinscombined toxicityIEC-6 cellsmetabolomicslipidomics |
| spellingShingle | Xinlu Wang Yanyang Xu Haiqi Yu Yushun Lu Yongzhong Qian Meng Wang Metabolomics and Lipidomics Reveal the Metabolic Disorders Induced by Single and Combined Exposure of Fusarium Mycotoxins in IEC-6 Cells Foods fusarium mycotoxins combined toxicity IEC-6 cells metabolomics lipidomics |
| title | Metabolomics and Lipidomics Reveal the Metabolic Disorders Induced by Single and Combined Exposure of Fusarium Mycotoxins in IEC-6 Cells |
| title_full | Metabolomics and Lipidomics Reveal the Metabolic Disorders Induced by Single and Combined Exposure of Fusarium Mycotoxins in IEC-6 Cells |
| title_fullStr | Metabolomics and Lipidomics Reveal the Metabolic Disorders Induced by Single and Combined Exposure of Fusarium Mycotoxins in IEC-6 Cells |
| title_full_unstemmed | Metabolomics and Lipidomics Reveal the Metabolic Disorders Induced by Single and Combined Exposure of Fusarium Mycotoxins in IEC-6 Cells |
| title_short | Metabolomics and Lipidomics Reveal the Metabolic Disorders Induced by Single and Combined Exposure of Fusarium Mycotoxins in IEC-6 Cells |
| title_sort | metabolomics and lipidomics reveal the metabolic disorders induced by single and combined exposure of fusarium mycotoxins in iec 6 cells |
| topic | fusarium mycotoxins combined toxicity IEC-6 cells metabolomics lipidomics |
| url | https://www.mdpi.com/2304-8158/14/2/230 |
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