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The Mycotoxin Deoxynivalenol Significantly Alters the Function and Metabolism of Bovine Kidney Epithelial Cells In Vitro

Bristol Veterinary School, University of Bristol, Langford, Bristol BS40 5DU, UK
Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, South Kensington Campus, London SW7 2AZ, UK
Rothamsted Research, North Wyke, Okehampton, Devon EX20 2SB, UK
Author to whom correspondence should be addressed.
These authors contributed equally to this study.
Toxins 2019, 11(10), 554;
Received: 18 June 2019 / Revised: 3 September 2019 / Accepted: 12 September 2019 / Published: 20 September 2019
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 1H 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-N-acetylglucosamine and decreased β-alanine, choline, creatine, taurine, and myo-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. View Full-Text
Keywords: mycotoxicosis; metabolic profiling; protein synthesis; cell cycle arrest mycotoxicosis; metabolic profiling; protein synthesis; cell cycle arrest
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Bailey, J.R.; Breton, J.; Panic, G.; Cogan, T.A.; Bailey, M.; Swann, J.R.; Lee, M.R.F. The Mycotoxin Deoxynivalenol Significantly Alters the Function and Metabolism of Bovine Kidney Epithelial Cells In Vitro. Toxins 2019, 11, 554.

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