Chan Wan, Cai Zongwei
Department of Chemistry, Hong Kong Baptist University, Kowloon, Hong Kong, SAR, China.
J Pharm Biomed Anal. 2008 Mar 13;46(4):757-62. doi: 10.1016/j.jpba.2007.11.042. Epub 2007 Dec 3.
Prolonged exposure to aristolochic acid (AA) has shown to pose rapid progressive renal fibrosis in Belgium women in a slimming regimen in the early 90s. We hypothesize that changes in metabolic profile could have occurred before symptoms were observed, which may allow early treatment. In this study, metabonomics was used for toxicology study of AA in rats. Liquid chromatography coupled with a hybrid quadrupole time-of-flight mass spectrometry (Qq-TOF) was used for the analysis of endogenous metabolites in rat urine samples. The difference in metabolic profiles between the control and the dosed rats was well observed by the principal component analysis (PCA) of the MS data. Significant changes of two metabolite markers, kynurenic acid and hippuric acid, were detected in the rat urine samples. The identification of potential biomarkers was performed by high-resolution mass measurement and MS-MS analyses on a Qq-TOF. We believe that metabolic profiling may act as a preclinical protocol for AA exposure before symptoms are observed.
20世纪90年代初，长期接触马兜铃酸（AA）已被证明会使采用减肥疗法的比利时女性迅速出现进行性肾纤维化。我们推测，在观察到症状之前可能已经发生了代谢谱变化，这或许能实现早期治疗。在本研究中，代谢组学被用于大鼠马兜铃酸的毒理学研究。液相色谱与混合四极杆飞行时间质谱（Qq-TOF）联用，用于分析大鼠尿液样本中的内源性代谢物。通过对质谱数据进行主成分分析（PCA），能很好地观察到对照大鼠和给药大鼠之间代谢谱的差异。在大鼠尿液样本中检测到两种代谢物标志物犬尿酸和马尿酸有显著变化。通过在Qq-TOF上进行高分辨率质量测量和MS-MS分析来鉴定潜在生物标志物。我们认为，代谢谱分析可能作为在观察到症状之前马兜铃酸暴露的临床前方案。
