The toxicity of acute exposure to T-2 toxin evaluated by the metabonomics technique
The toxicity of acute exposure to T-2 toxin evaluated by the metabonomics technique
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代谢组学技术评价T-2毒素急性暴露毒性
DOI：
10.1039/c4mb00622d
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发表时间：
2015-01-01
影响因子：
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通讯作者：
Wang, Yulan
中科院分区：
文献类型：
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作者：
Wan, Qianfen;Wu, Guangyao;Wang, Yulan
T-2毒素是谷物和动物饲料中常见的污染物，由于其高毒性，对人类和动物健康的威胁日益严重。研究T-2毒素的全身效应对评价其毒性和促进食品安全评价具有重要意义。在我们的研究中，通过灌胃给大鼠以0、0.5、2.0和4.0 mg kg（-1）体重的单剂量T-2毒素。通过核磁共振谱法获得体液和多器官代谢谱，并采用多元数据分析方法进行分析。结果表明，低剂量和中等剂量的T-2毒素仅影响尿代谢组，而高剂量的T-2毒素诱导尿液和多个器官的代谢改变。这些变化包括膜代谢物、三羧酸循环中间体、一系列氨基酸、核苷和核苷酸水平的改变。T-2毒素暴露损害脾脏功能，引起免疫毒性，抑制蛋白质和DNA的生物合成。此外，T-2毒素还引起氧化应激、能量代谢紊乱和肠道微生物群紊乱。我们的工作提供了对T-2毒性的全面了解，并揭示了代谢组学在评估有毒化合物影响方面的巨大潜力。
T-2 toxin is a common contaminant in grains and animal feedstuff, which becomes an increasing threat to human and animal health due to its high toxicity. Investigating the systemic effects of T-2 toxin is important to evaluate the toxicity and facilitate the assessment of food safety. In our investigation, rats were treated with a single dose of T-2 toxin at dosage levels of 0, 0.5, 2.0 and 4.0 mg kg(-1) body weight via gavage. The metabolic profiles of body fluids and multiple organs were obtained by NMR spectroscopy and analyzed by multivariate data analysis methods. The results showed that low and moderate doses of T-2 toxin only influenced the urinary metabonomes, while a high dose of T-2 toxin induced metabolic alterations in urine and multiple organs. These changes included alterations in the levels of membrane metabolites, TCA cycle intermediates, a range of amino acids, nucleosides and nucleotides. T-2 toxin exposure impaired spleen function, causing immunotoxicity, and inhibited protein and DNA biosynthesis. In addition, T-2 toxin also caused oxidative stress and disturbance in energy metabolism and gut microbiome. Our work provided a comprehensive insight into T-2 toxicity and revealed the great potential of metabonomics in assessing the impact of a toxic compound.