Exposure to the mycotoxin deoxynivalenol reduces the transport of conjugated bile acids by intestinal Caco-2 cells
| العنوان: | Exposure to the mycotoxin deoxynivalenol reduces the transport of conjugated bile acids by intestinal Caco-2 cells |
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| المؤلفون: | Jingxuan Wang, Wouter Bakker, Weijia Zheng, Laura de Haan, Ivonne M. C. M. Rietjens, Hans Bouwmeester |
| المصدر: | Archives of Toxicology, 96(5), 1473-1482 Archives of Toxicology 96 (2022) 5 |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Bile acid transporters, Health, Toxicology and Mutagenesis, General Medicine, Mycotoxins, Toxicology, digestive system, Deoxynivalenol, Bile Acids and Salts, Intestines, Humans, Caco-2 Cells, Trichothecenes, Conjugated bile acids, Bile acid reabsorption, Toxicologie, VLAG |
| الوصف: | Conjugated bile acids are synthesized in liver and subsequently secreted into the intestinal lumen from which they are actively reabsorbed and transported back to liver. The efficient enterohepatic circulation of conjugated bile acids is important to maintain homeostasis. The mycotoxin deoxynivalenol (DON) is a fungal secondary metabolite that contaminates cereal food. Upon human exposure, it can cause intestinal dysfunction. We explored the effects of DON exposure on the intestinal absorption of conjugated bile acids and the expression of bile acid transporters using an in vitro model based on Caco-2 cell layers grown in transwells. Our study shows that the transport rate of taurocholic acid (TCA) is decreased after 48-h pre-exposure of the Caco-2 cells to 2 µM DON, which is a realistic intestinal DON concentration. Exposure to DON downregulates expression of the genes coding for the apical sodium-dependent bile acid transporter (ASBT), the ileal bile acid-binding protein (IBABP) and the organic solute transporter α (OSTα), and it counteracts the agonist activity of Farnesoid X receptor (FXR) agonist GW4064 on these genes. In addition, the transport of ten taurine or glycine-conjugated bile acids in a physiological relevant mixture by the intestinal Caco-2 cell layers was decreased after pre-exposure of the cells to DON, pointing at a potential for DON-mediated accumulation of the conjugated bile acids at the intestinal luminal side. Together the results reveal that DON inhibits intestinal bile acid reabsorption by reducing the expression of bile acid transporters thereby affecting bile acid intestinal kinetics, leading to bile acid malabsorption in the intestine. Our study provides new insights into the hazards of DON exposure. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0340-5761 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4e32d66e427e75a4c8d172a33b5ab2e9Test https://doi.org/10.1007/s00204-022-03256-8Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....4e32d66e427e75a4c8d172a33b5ab2e9 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 03405761 |
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