Discovery of safety biomarkers for realgar in rat urine using UFLC-IT-TOF/MS and 1H NMR based metabolomics
Discovery of safety biomarkers for realgar in rat urine using UFLC-IT-TOF/MS and 1H NMR based metabolomics
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DOI：
10.1007/s00216-013-6842-0
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发表时间：
2013-05-01
影响因子：
4.3
通讯作者：
Zhang, Zunjian
中科院分区：
文献类型：
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作者：
Huang, Yin;Tian, Yuan;Zhang, Zunjian
作为一种砷，雄黄 (As4S4) 被认为是一种毒药，但矛盾的是它又是一种治疗剂。然而，人们对雄黄的毒性和治疗效果所伴随的精确生化变化缺乏全面的了解。使用超快液相色谱 (UFLC) 与离子阱飞行时间质谱 (IT-TOF/MS) 和基于 H-1 NMR 光谱的代谢组学方法相结合，我们能够描绘雄黄治疗大鼠尿液样本中显着改变的代谢物。对液相色谱LC/MS和NMR技术的平台稳定性进行了系统研究，并仔细优化了数据处理方法。我们的结果表明氨基酸代谢、柠檬酸循环、胆碱代谢和卟啉代谢存在显着扰动。提出了 36 种代谢物作为与雄黄引起的干扰相关的潜在安全生物标志物，并且甘氨酸和丝氨酸预计将作为与雄黄引起的干扰相关的代谢途径中的中心接触点。建立的基于 LC/MS 和 NMR 的代谢组学方法为雄黄对大鼠的生化作用提供了系统和整体的看法，并且将来可能用于研究其他药物或外源性物质。
As an arsenical, realgar (As4S4) is known as a poison and paradoxically as a therapeutic agent. However, a complete understanding of the precise biochemical alterations accompanying the toxicity and therapy effects of realgar is lacking. Using a combined ultrafast liquid chromatography (UFLC) coupled with ion trap time-of-flight mass spectrometry (IT-TOF/MS) and H-1 NMR spectroscopy based metabolomics approach, we were able to delineate significantly altered metabolites in the urine samples of realgar-treated rats. The platform stability of the liquid chromatography LC/MS and NMR techniques was systematically investigated, and the data processing method was carefully optimized. Our results indicate significant perturbations in amino acid metabolism, citric acid cycle, choline metabolism, and porphyrin metabolism. Thirty-six metabolites were proposed as potential safety biomarkers related to disturbances caused by realgar, and glycine and serine are expected to serve as the central contacts in the metabolic pathways related to realgar-induced disturbance. The LC/MS and NMR based metabolomics approach established provided a systematic and holistic view of the biochemical effects of realgar on rats, and might be employed to investigate other drugs or xenobiotics in the future.