{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T15:28:53Z","timestamp":1791646133184,"version":"4.3.4"},"reference-count":49,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2019,9,20]],"date-time":"2019-09-20T00:00:00Z","timestamp":1568937600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/M006409\/1"],"award-info":[{"award-number":["BB\/M006409\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>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\u2013Darby 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 \u03b2-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.<\/jats:p>","DOI":"10.3390\/toxins11100554","type":"journal-article","created":{"date-parts":[[2019,9,20]],"date-time":"2019-09-20T10:48:14Z","timestamp":1568976494000},"page":"554","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["The Mycotoxin Deoxynivalenol Significantly Alters the Function and Metabolism of Bovine Kidney Epithelial Cells In Vitro"],"prefix":"10.3390","volume":"11","author":[{"given":"Jennifer R.","family":"Bailey","sequence":"first","affiliation":[{"name":"Bristol Veterinary School, University of Bristol, Langford, Bristol BS40 5DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Breton","sequence":"additional","affiliation":[{"name":"Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, South Kensington Campus, London SW7 2AZ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6423-3183","authenticated-orcid":false,"given":"Gordana","family":"Panic","sequence":"additional","affiliation":[{"name":"Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, South Kensington Campus, London SW7 2AZ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tristan A.","family":"Cogan","sequence":"additional","affiliation":[{"name":"Bristol Veterinary School, University of Bristol, Langford, Bristol BS40 5DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Bailey","sequence":"additional","affiliation":[{"name":"Bristol Veterinary School, University of Bristol, Langford, Bristol BS40 5DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6485-4529","authenticated-orcid":false,"given":"Jonathan R.","family":"Swann","sequence":"additional","affiliation":[{"name":"Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, South Kensington Campus, London SW7 2AZ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R. F.","family":"Lee","sequence":"additional","affiliation":[{"name":"Bristol Veterinary School, University of Bristol, Langford, Bristol BS40 5DU, UK"},{"name":"Rothamsted Research, North Wyke, Okehampton, Devon EX20 2SB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,9,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.tvjl.2007.12.034","article-title":"The role of mycotoxins in the health and performance of dairy cows","volume":"176","year":"2008","journal-title":"Vet. J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3057","DOI":"10.3390\/toxins7083057","article-title":"Review on mycotoxin issues in ruminants: Occurrence in forages, effects of mycotoxin ingestion on health status and animal performance and practical strategies to counteract their negative effects","volume":"7","author":"Gallo","year":"2015","journal-title":"Toxins"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2570","DOI":"10.3390\/ijms9122570","article-title":"Zearalenone and reproductive function in farm animals","volume":"9","author":"Minervini","year":"2008","journal-title":"Int. J. Mol. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Bertero, A., Moretti, A., Spicer, L.J., and Caloni, F. (2018). Fusarium molds and mycotoxins: Potential species-specific effects. Toxins, 10.","DOI":"10.3390\/toxins10060244"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1080\/02652030500058320","article-title":"Immunotoxicological risk of mycotoxins for domestic animals","volume":"22","author":"Oswald","year":"2005","journal-title":"Food Addit. Contam."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"365","DOI":"10.2478\/v10181-012-0055-x","article-title":"Zearalenone and deoxynivalenol mycotoxicosis in dairy cattle herds","volume":"15","author":"Marczuk","year":"2012","journal-title":"Pol. J. Vet. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1007\/s11046-005-2877-x","article-title":"Patulin produced by an Aspergillus clavatus isolated from feed containing malting residues associated with a lethal neurotoxicosis in cattle","volume":"158","author":"Maas","year":"2004","journal-title":"Mycopathology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"471","DOI":"10.5958\/0974-181X.2015.00048.7","article-title":"Occurrence, prevention and limitation of mycotoxins in feeds","volume":"1515","author":"Abdallah","year":"2015","journal-title":"Anim. Nutr. Feed Technol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.3168\/jds.S0022-0302(82)82374-6","article-title":"Responses of dairy cows to dietary aflatoxin: Feed intake and yield, toxin content, and quality of milk of cows treated with pure and impure aflatoxin","volume":"65","author":"Applebaum","year":"1982","journal-title":"J. Dairy Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1071\/AN11205","article-title":"Effect of mycotoxin deactivator product supplementation on dairy cows","volume":"52","author":"Kiyothong","year":"2012","journal-title":"Anim. Prod. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.anifeedsci.2007.06.002","article-title":"An historical overview of field disease outbreaks known or suspected to be caused by consumption of feeds contaminated with Fusarium toxins","volume":"137","author":"Morgavi","year":"2007","journal-title":"Anim. Feed Sci. Technol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.jscs.2010.06.006","article-title":"Impact of mycotoxins on humans and animals","volume":"15","author":"Zain","year":"2011","journal-title":"J. Saudi Chem. Soc."},{"key":"ref_13","first-page":"212","article-title":"Mycotoxins in foods\u2014Occurrence, health and economic significance and food control measures","volume":"108","author":"Vasanthi","year":"1998","journal-title":"Indian J. Med. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1365-2494.2012.00891.x","article-title":"The aerobic stability of silage: Key findings and recent developments","volume":"6868","author":"Wilkinson","year":"2013","journal-title":"Grass Forage Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/S0377-8401(99)00059-0","article-title":"Fusarium mycotoxins: A review of global implications for animal health, welfare and productivity","volume":"80","author":"Placinta","year":"1999","journal-title":"Anim. Feed Sci. Technol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3","DOI":"10.22358\/jafs\/66965\/2005","article-title":"Relevance of the Fusarium toxins deoxynivalenol and zearalenone in ruminant nutrition. A review","volume":"14","author":"Seeling","year":"2005","journal-title":"J. Anim. Feed Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1111\/gfs.12265","article-title":"Silage and total mixed ration hygienic quality on commercial farms: Implications for animal production","volume":"72","author":"Cogan","year":"2017","journal-title":"Grass Forage Sci."},{"key":"ref_18","unstructured":"(2018, October 05). HY-SIL Collaborators, HY-SIL Project Farm Study on Silage and Animal Health. Available online: http:\/\/www.bovmycotox.co.uk\/wp-content\/uploads\/2015\/08\/MycotoxinFarmSurvey2015.pdf."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/(SICI)1097-0010(199805)77:1<1::AID-JSFA9>3.0.CO;2-4","article-title":"Occurrence and significance of mycotoxins in forage crops and silage: A review","volume":"77","author":"Scudamore","year":"1998","journal-title":"J. Sci. Food Agric."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1080\/10408390500436185","article-title":"Strategies to prevent mycotoxin contamination of food and animal feed: A review","volume":"46","author":"Kabak","year":"2006","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_21","first-page":"94","article-title":"Deoxynivalenol and its toxicity","volume":"33","author":"Sobrova","year":"2010","journal-title":"Interdiscip. Toxicol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"663","DOI":"10.3390\/toxins4090663","article-title":"A three-year survey on the worldwide occurrence of mycotoxins in feedstuffs and feed","volume":"4","author":"Rodrigues","year":"2012","journal-title":"Toxins"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1139\/w00-045","article-title":"Effects of the Fusarium spp. mycotoxins fusaric acid and deoxynivalenol on the growth of Ruminococcus albus and Methanobrevibacter ruminantium","volume":"46","author":"May","year":"2000","journal-title":"Can. J. Microbiol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Novak, B., Vatzia, E., Springler, A., Pierron, A., Gerner, W., Reisinger, N., Hessenberger, S., Schatzmayr, G., and Mayer, E. (2018). Bovine peripheral blood mononuclear cells are more sensitive to deoxynivalenol than those derived from poultry and swine. Toxins, 10.","DOI":"10.3390\/toxins10040152"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1093\/biolre\/iox127","article-title":"The mycotoxin metabolite deepoxy-deoxynivalenol increases apoptosis and decreases steroidogenesis in bovine ovarian theca cells","volume":"97","author":"Estienne","year":"2017","journal-title":"Biol. Reprod."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.toxicon.2015.11.018","article-title":"In vitro effects of deoxynivalenol and zearalenone major metabolites alone and combined, on cell proliferation, steroid production and gene expression in bovine small-follicle granulosa cells","volume":"109","author":"Pizzo","year":"2016","journal-title":"Toxicon"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1007\/s00204-010-0579-8","article-title":"Deoxynivalenol: Mechanisms of action, human exposure, and toxicological relevance","volume":"84","author":"Pestka","year":"2010","journal-title":"Arch. Toxicol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"13985","DOI":"10.1074\/jbc.274.20.13985","article-title":"Trichothecene mycotoxins trigger a ribotoxic stress response that activates c-Jun N-terminal kinase and p38 mitogen-activated protein kinase and induces apoptosis","volume":"274","author":"Shifrin","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1093\/toxsci\/kfg148","article-title":"Role of double-stranded RNA-Activated protein kinase R (PKR) in deoxynivalenol-induced ribotoxic stress response","volume":"74","author":"Zhou","year":"2003","journal-title":"Toxicol. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1093\/toxsci\/kfn111","article-title":"Comparative induction of 28S ribosomal RNA cleavage by ricin and the trichothecenes deoxynivalenol and T-2 toxin in the macrophage","volume":"105","author":"Li","year":"2008","journal-title":"Toxicol. Sci."},{"key":"ref_31","unstructured":"Lodish, H., Berk, A., Zipursky, S.L., Matsudaira, P., Baltimore, D., and Darnell, J. (2000). MAP kinase pathways, Molecular Cell Biology."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.tox.2007.10.002","article-title":"Ribotoxic mycotoxin deoxynivalenol induces G2\/M cell cycle arrest via p21Cip\/WAF1 mRNA stabilization in human epithelial cells","volume":"243","author":"Yang","year":"2008","journal-title":"Toxicology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.etap.2013.11.015","article-title":"Evaluation of deoxynivalenol-induced toxic effects on DF-1 cells in vitro: Cell-Cycle arrest, oxidative stress, and apoptosis","volume":"37","author":"Li","year":"2014","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Diesing, A.-K., Nossol, C., D\u00e4nicke, S., Walk, N., Post, A., Kahlert, S., Rothk\u00f6tter, H.-J., and Kluess, J. (2011). Vulnerability of polarised intestinal porcine epithelial cells to mycotoxin deoxynivalenol depends on the route of application. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0017472"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Moonen, L., D\u2019Haese, P.C., and Vervaet, B.A. (2018). Epithelial cell cycle behaviour in the injured kidney. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19072038"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.freeradbiomed.2010.03.016","article-title":"Lutein protects HT-29 cells against Deoxynivalenol-induced oxidative stress and apoptosis: Prevention of NF-\u03baB nuclear localization and down regulation of NF-\u03baB and Cyclo-Oxygenase\u20142 expression","volume":"49","author":"Krishnaswamy","year":"2010","journal-title":"Free Radic. Biol. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.fct.2014.06.027","article-title":"Role of oxidative stress in deoxynivalenol induced toxicity","volume":"72","author":"Mishra","year":"2014","journal-title":"Food Chem. Toxicol."},{"key":"ref_38","unstructured":"Klimanskaya, I., and Lanza, R. (2006). Kidney epithelial cells. Methods in Enzymology, Academic Press."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1152\/physiol.00009.2009","article-title":"What\u2019s new about osmotic regulation of glycerophosphocholine","volume":"24","author":"Gallazzini","year":"2009","journal-title":"Physiology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"C804","DOI":"10.1152\/ajpcell.1997.272.3.C804","article-title":"Osmotic regulation of amino acids and system A transport in Madin-Darby canine kidney cells","volume":"272","author":"Horio","year":"1997","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1186\/1423-0127-17-S1-S4","article-title":"Taurine and the renal system","volume":"17","author":"Chesney","year":"2010","journal-title":"J. Biomed. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"F137","DOI":"10.1152\/ajprenal.1993.265.1.F137","article-title":"Polarity of taurine transport in cultured renal epithelial cell lines: LLC-PK1 and MDCK","volume":"265","author":"Jones","year":"1993","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.fct.2013.01.042","article-title":"Cytoprotective effect of epigallocatechin-3-gallate against deoxynivalenol-induced toxicity through anti-oxidative and anti-inflammatory mechanisms in HT-29 cells","volume":"56","author":"Kalaiselvi","year":"2013","journal-title":"Food Chem. Toxicol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.acthis.2018.02.005","article-title":"Tetrazolium salts and formazan products in Cell Biology: Viability assessment, fluorescence imaging, and labeling perspectives","volume":"120","author":"Stockert","year":"2018","journal-title":"Acta Histochem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/S1387-2656(05)11004-7","article-title":"Tetrazolium dyes as tools in cell biology: New insights into their cellular reduction","volume":"11","author":"Berridge","year":"2005","journal-title":"Biotechnol. Annu. Rev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1042\/bj3610417","article-title":"Carnitine biosynthesis in mammals","volume":"361","author":"Vaz","year":"2002","journal-title":"Biochem. J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1681\/ASN.2012080855","article-title":"Mechanisms of hypoxia responses in renal tissue","volume":"24","author":"Haase","year":"2013","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1681\/ASN.2014050457","article-title":"Disruption of renal tubular mitochondrial quality control by myo-inositol oxygenase in diabetic kidney disease","volume":"26","author":"Zhan","year":"2015","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_49","first-page":"e3491","article-title":"Analysis of cell cycle position in mammalian cells","volume":"59","author":"Cecchini","year":"2012","journal-title":"J. Vis. Exp. JoVE"}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/11\/10\/554\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:22:29Z","timestamp":1760188949000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/11\/10\/554"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9,20]]},"references-count":49,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2019,10]]}},"alternative-id":["toxins11100554"],"URL":"https:\/\/doi.org\/10.3390\/toxins11100554","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,9,20]]}}}