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.
Toxins (Basel). 2019 Sep 20;11(10):554. doi: 10.3390/toxins11100554.
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 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--acetylglucosamine and decreased β-alanine, choline, creatine, taurine, and -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.
牛真菌毒素中毒是一种由真菌毒素摄入引起的疾病。它与慢性症状有关，如生长速度和产奶量下降，并给奶牛养殖业造成重大经济损失。真菌毒素脱氧雪腐镰刀菌烯醇（DON）、玉米赤霉烯酮（ZEN）和伏马菌素 B1（FB1）在牛饲料中很常见。棒曲霉素（PA）是一种常见的草青贮污染物，但也存在于谷物中。这些真菌毒素在低浓度下对细胞功能的影响尚未得到很好的理解。本研究使用 Madin-Darby 牛肾细胞评估了这些真菌毒素对细胞的反应，测量了细胞毒性、从头蛋白质合成、细胞增殖、细胞周期分析以及通过 H NMR 光谱进行代谢谱分析。DON、ZEN 和 PA 诱导细胞毒性，PA 和 FB1 诱导存活细胞代谢活性降低。只有 DON 被发现对代谢谱有显著影响，暴露细胞显示细胞内氨基酸、乳酸、2-氧戊二酸、3-羟基丁酸和 UDP-乙酰葡萄糖胺增加，而β-丙氨酸、胆碱、肌酸、牛磺酸和肌醇减少。暴露于 DON 的细胞的蛋白质合成也减少。DON 以前被记录为一种核糖毒素；这里的结果表明，DON 暴露导致牛细胞蛋白质合成减少，同时细胞内前体物质积累。细胞增殖也被阻止而没有引起细胞凋亡。DON 可能会引发牛细胞缺氧、高渗和核糖毒性反应，这些反应导致暴露牛的生产力下降。
