The Mycotoxin Deoxynivalenol Significantly Alters the Function and Metabolism of Bovine Kidney Epithelial Cells In Vitro
Bovine mycotoxicosis is a disorder caused by the ingestion of fungal toxins. It is associated with chronic signs, such as reduced growth rate and milk yield, and causes significant economic cost to the dairy industry. The mycotoxins deoxynivalenol (DON), zearalenone (ZEN), and fumonisin B1 (FB1) are...
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MDPI AG
2019-09-01
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author | Jennifer R. Bailey Jonathan Breton Gordana Panic Tristan A. Cogan Michael Bailey Jonathan R. Swann Michael R. F. Lee |
author_facet | Jennifer R. Bailey Jonathan Breton Gordana Panic Tristan A. Cogan Michael Bailey Jonathan R. Swann Michael R. F. Lee |
author_sort | Jennifer R. Bailey |
collection | DOAJ |
description | Bovine mycotoxicosis is a disorder caused by the ingestion of fungal toxins. It is associated with chronic signs, such as reduced growth rate and milk yield, and causes significant economic cost to the dairy industry. The mycotoxins deoxynivalenol (DON), zearalenone (ZEN), and fumonisin B1 (FB1) are commonly found in grain fed to cattle. Patulin (PA) is a common grass silage contaminant but is also found in grain. The effects of these mycotoxins on cellular function at low concentrations are not well understood. Using Madin−Darby bovine kidney cells we evaluated the cellular response to these mycotoxins, measuring cytotoxicity, de novo protein synthesis, cell proliferation, cell cycle analysis, and also metabolic profiling by <sup>1</sup>H NMR spectroscopy. DON, ZEN, and PA induced cytotoxicity, and PA and FB1 induced a decrease in metabolic activity in surviving cells. DON was the only mycotoxin found to have a significant effect on the metabolic profile, with exposed cells showing increased cellular amino acids, lactate, 2-oxoglutarate, 3-hydroxybutyrate, and UDP-<i>N</i>-acetylglucosamine and decreased β-alanine, choline, creatine, taurine, and <i>myo</i>-inositol. Cells exposed to DON also showed reductions in protein synthesis. DON has previously been documented as being a ribotoxin; the results here suggest that exposure of bovine cells to DON causes a decrease in protein synthesis with corresponding cellular accumulation of precursors. Cell proliferation was also arrested without causing apoptosis. It is likely that exposure triggers hypoxic, hypertonic, and ribotoxic responses in bovine cells, and that these responses contribute to reduced productivity in exposed cattle. |
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spelling | doaj.art-f367b3bf36d54eaba880f31ca8a9c4c72022-12-22T04:19:52ZengMDPI AGToxins2072-66512019-09-01111055410.3390/toxins11100554toxins11100554The Mycotoxin Deoxynivalenol Significantly Alters the Function and Metabolism of Bovine Kidney Epithelial Cells In VitroJennifer R. Bailey0Jonathan Breton1Gordana Panic2Tristan A. Cogan3Michael Bailey4Jonathan R. Swann5Michael R. F. Lee6Bristol Veterinary School, University of Bristol, Langford, Bristol BS40 5DU, UKDepartment of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, South Kensington Campus, London SW7 2AZ, UKDepartment of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, South Kensington Campus, London SW7 2AZ, UKBristol Veterinary School, University of Bristol, Langford, Bristol BS40 5DU, UKBristol Veterinary School, University of Bristol, Langford, Bristol BS40 5DU, UKDepartment of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, South Kensington Campus, London SW7 2AZ, UKBristol Veterinary School, University of Bristol, Langford, Bristol BS40 5DU, UKBovine mycotoxicosis is a disorder caused by the ingestion of fungal toxins. It is associated with chronic signs, such as reduced growth rate and milk yield, and causes significant economic cost to the dairy industry. The mycotoxins deoxynivalenol (DON), zearalenone (ZEN), and fumonisin B1 (FB1) are commonly found in grain fed to cattle. Patulin (PA) is a common grass silage contaminant but is also found in grain. The effects of these mycotoxins on cellular function at low concentrations are not well understood. Using Madin−Darby bovine kidney cells we evaluated the cellular response to these mycotoxins, measuring cytotoxicity, de novo protein synthesis, cell proliferation, cell cycle analysis, and also metabolic profiling by <sup>1</sup>H NMR spectroscopy. DON, ZEN, and PA induced cytotoxicity, and PA and FB1 induced a decrease in metabolic activity in surviving cells. DON was the only mycotoxin found to have a significant effect on the metabolic profile, with exposed cells showing increased cellular amino acids, lactate, 2-oxoglutarate, 3-hydroxybutyrate, and UDP-<i>N</i>-acetylglucosamine and decreased β-alanine, choline, creatine, taurine, and <i>myo</i>-inositol. Cells exposed to DON also showed reductions in protein synthesis. DON has previously been documented as being a ribotoxin; the results here suggest that exposure of bovine cells to DON causes a decrease in protein synthesis with corresponding cellular accumulation of precursors. Cell proliferation was also arrested without causing apoptosis. It is likely that exposure triggers hypoxic, hypertonic, and ribotoxic responses in bovine cells, and that these responses contribute to reduced productivity in exposed cattle.https://www.mdpi.com/2072-6651/11/10/554mycotoxicosismetabolic profilingprotein synthesiscell cycle arrest |
spellingShingle | Jennifer R. Bailey Jonathan Breton Gordana Panic Tristan A. Cogan Michael Bailey Jonathan R. Swann Michael R. F. Lee The Mycotoxin Deoxynivalenol Significantly Alters the Function and Metabolism of Bovine Kidney Epithelial Cells In Vitro Toxins mycotoxicosis metabolic profiling protein synthesis cell cycle arrest |
title | The Mycotoxin Deoxynivalenol Significantly Alters the Function and Metabolism of Bovine Kidney Epithelial Cells In Vitro |
title_full | The Mycotoxin Deoxynivalenol Significantly Alters the Function and Metabolism of Bovine Kidney Epithelial Cells In Vitro |
title_fullStr | The Mycotoxin Deoxynivalenol Significantly Alters the Function and Metabolism of Bovine Kidney Epithelial Cells In Vitro |
title_full_unstemmed | The Mycotoxin Deoxynivalenol Significantly Alters the Function and Metabolism of Bovine Kidney Epithelial Cells In Vitro |
title_short | The Mycotoxin Deoxynivalenol Significantly Alters the Function and Metabolism of Bovine Kidney Epithelial Cells In Vitro |
title_sort | mycotoxin deoxynivalenol significantly alters the function and metabolism of bovine kidney epithelial cells in vitro |
topic | mycotoxicosis metabolic profiling protein synthesis cell cycle arrest |
url | https://www.mdpi.com/2072-6651/11/10/554 |
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