Chen Minjun, Su Mingming, Zhao Liping, Jiang Jian, Liu Ping, Cheng Jiye, Lai Yijiang, Liu Yumin, Jia Wei
School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200030, China.
J Proteome Res. 2006 Apr;5(4):995-1002. doi: 10.1021/pr050404w.
This paper describes a metabonomic study characterizing the nephrotoxicity induced by aristolochic acid (AA), a suspected kidney toxicant. For these studies, we examined the biochemical compositions of AA-treated rat urine using LC-MS and pattern recognition methods. The biochemical and histological patterns of rat groups treated with different AA sources showed distinct differences from those of the control group. Certain metabolic pathways, such as homocysteine formation and the folate cycle were significantly accelerated, while others, including arachidonic acid biosynthesis, were decreased. A subset-validation procedure using linear discriminant analysis (LDA) and selected predictive variables indicated that approximately 95% of the treated and nontreated rat urine samples were classified correctly into their respective treatment groups. The results suggested that this metabonomic approach is a promising methodology for the rapid in vivo screening of nephrotoxicity associated with ingesting multi-ingredient medicinal herb supplements, and provides a valid method for comprehending the chemical-induced perturbations in the metabolic network and the networked lesions.
本文描述了一项代谢组学研究，该研究对疑似肾毒物马兜铃酸（AA）诱导的肾毒性进行了表征。在这些研究中，我们使用液相色谱-质谱联用（LC-MS）和模式识别方法检测了经AA处理的大鼠尿液的生化成分。用不同AA来源处理的大鼠组的生化和组织学模式与对照组有明显差异。某些代谢途径，如同型半胱氨酸形成和叶酸循环显著加速，而其他途径，包括花生四烯酸生物合成则减少。使用线性判别分析（LDA）和选定预测变量的子集验证程序表明，约95%的处理组和未处理组大鼠尿液样本被正确分类到各自的处理组中。结果表明，这种代谢组学方法是一种很有前景的方法，可用于快速体内筛选与摄入多成分药用草药补充剂相关的肾毒性，并为理解化学物质诱导的代谢网络扰动和网络损伤提供了一种有效的方法。
