Department of Pharmaceutical Analysis, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, 110016, PR China.
Rapid Commun Mass Spectrom. 2011 Sep 30;25(18):2633-40. doi: 10.1002/rcm.5163.
A metabonomic approach based on ultra-performance liquid chromatography coupled to mass spectrometry (UPLC/MS) was used to study the nephrotoxicity of rhizoma alismatis (RA) in rats. Potential biomarkers of RA toxicity were identified and the toxicological mechanism is discussed. Urine samples were collected from control and treated rats at various stages and analyzed by UPLC/MS in positive ionization mode. Histopathological analysis was used to evaluate renal function. The differences in the metabolic profiles of the control and treated rats were clearly distinguishable with principal components analysis (PCA) of the chromatographic data, and significant changes in 13 metabolite biomarkers were detected in the urine. This metabonomic method combined with PCA could discriminate the treated rats from the control rats on days 60, 120, and 180 after treatment, before serious organic renal damage was apparent on day 180 with histopathology. This research indicates that UPLC/MS-based metabonomic analysis of urine samples can be used to predict the chronic nephrotoxicity induced by rhizoma alismatis.
基于超高效液相色谱-质谱联用（UPLC/MS）的代谢组学方法用于研究泽泻在大鼠体内的肾毒性。鉴定了泽泻毒性的潜在生物标志物，并探讨了其毒理学机制。收集对照和处理大鼠在不同阶段的尿液样本，并在正离子模式下进行 UPLC/MS 分析。采用组织病理学分析评估肾功能。通过对色谱数据进行主成分分析（PCA），可以清楚地区分对照和处理大鼠的代谢谱差异，并在尿液中检测到 13 种代谢标志物的显著变化。这种代谢组学方法与 PCA 相结合，可以在第 180 天组织病理学出现明显的器质性肾损伤之前，在第 60、120 和 180 天分别区分处理大鼠和对照大鼠。本研究表明，基于 UPLC/MS 的尿液样本代谢组学分析可用于预测泽泻引起的慢性肾毒性。
