Chan Wan, Lee Kim-Chung, Liu Ning, Wong Ricky N S, Liu Huwei, Cai Zongwei
Department of Chemistry, Hong Kong Baptist University, Hong Kong SAR, China.
Rapid Commun Mass Spectrom. 2008;22(6):873-80. doi: 10.1002/rcm.3438.
The toxic effects of oral administrations of nephrotoxic and carcinogenic aristolochic acid (AA) to male Sprague-Dawley rats were investigated by using high-performance liquid chromatography coupled with a quadrupole time-of-flight mass spectrometer. Analysis of the urine and plasma samples revealed distinct changes in the biochemical patterns in the AA-dosed rats. After peak finding and alignment, principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) were used for multivariate data analysis. Potential biomarkers were studied by high-resolution mass spectrometry (MS) and tandem mass spectrometry (MS/MS) analyses. The MS/MS spectra of all endogenous metabolites satisfying the pre-defined criteria were acquired in a single information-dependent acquisition (IDA) analysis, demonstrating that IDA was an efficient approach for structural elucidation in metabonomic studies. Citric acid and a glucuronide-containing metabolite were observed as potential biomarkers in rat urine. A significant increase in plasma creatinine concentration was also observed in the AA-dosed rats, which indicated that AA induced an adverse effect on the renal clearance function.
采用高效液相色谱-四极杆飞行时间质谱联用技术，研究了口服肾毒性和致癌性马兜铃酸（AA）对雄性斯普拉格-道利大鼠的毒性作用。对尿液和血浆样本的分析显示，给予AA的大鼠生化模式有明显变化。在进行峰识别和峰对齐后，主成分分析（PCA）和偏最小二乘判别分析（PLS-DA）用于多变量数据分析。通过高分辨率质谱（MS）和串联质谱（MS/MS）分析研究潜在生物标志物。在单次信息依赖采集（IDA）分析中获得了所有满足预定义标准的内源性代谢物的MS/MS谱，表明IDA是代谢组学研究中结构解析的有效方法。柠檬酸和一种含葡萄糖醛酸的代谢物被观察到是大鼠尿液中的潜在生物标志物。给予AA的大鼠血浆肌酐浓度也显著升高，这表明AA对肾脏清除功能产生了不良影响。
