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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Main Authors: Jennifer R. Bailey, Jonathan Breton, Gordana Panic, Tristan A. Cogan, Michael Bailey, Jonathan R. Swann, Michael R. F. Lee
Format: Article
Language:English
Published: MDPI AG 2019-09-01
Series:Toxins
Subjects:
Online Access:https://www.mdpi.com/2072-6651/11/10/554
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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&#8722;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 &#946;-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&#8722;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 &#946;-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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