An integrated metabonomic method for profiling of metabolic changes in carbon tetrachloride induced rat urine
An integrated metabonomic method for profiling of metabolic changes in carbon tetrachloride induced rat urine
复制标题
用于分析四氯化碳诱导的大鼠尿液代谢变化的综合代谢组学方法
DOI：
10.1016/j.tox.2008.11.018
复制
发表时间：
2009-02-27
期刊：
影响因子：
4.5
通讯作者：
Liu, Changxiao
中科院分区：
文献类型：
--
作者：
Lin, Yanping;Si, Duanyun;Liu, Changxiao
四氯化碳（CCl 4）是一种众所周知的诱导化学性肝损伤的模型化合物。本工作在Wistar大鼠模型中以1 ml/kg的单次剂量描述了CCl_4诱导的肝毒性代谢紊乱。在本实验中，对雄性大鼠进行了为期7天的连续尿液收集。通过血液生化和组织病理学检查确定肝毒性的特异性变化。同时，开发了一种基于液相色谱-质谱联用（LC-MS）的综合分析方法，以绘制尿液中的代谢反应。目前基于LC-MS的代谢组学方法表明，尿液中有23种内源性代谢物作为与CCl 4诱导的肝毒性相关的生物标志物。根据鉴定的代谢产物讨论了CCl 4干扰代谢途径的潜在调节。本研究证明了基于LC-MS的代谢组学在绘制毒理学代谢反应图谱方面的巨大潜力。(C)2008爱思唯尔爱尔兰有限公司保留所有权利。
Carbon tetrachloride (CCl4) is a well-known model compound for inducing chemical hepatic injury. This work characterizes the metabolism disorders of hepatotoxicity induced by CCl4 in a Wistar rat model with a single dosage of 1 ml/kg. A seven-day long continuous collection of urine was performed in male rats in this experiment. Blood biochemistry and histopathology were examined to identify specific changes of liver hepatotoxicity. At the same time, an integrated analytical approach based on liquid chromatography coupled with mass spectrometry (LC-MS) was developed to map the metabolic response in urine. The current metabonomic approach based on LC-MS indicated 23 endogenous metabolites as biomarkers in urine associated with the hepatotoxicity induced by CCl4. The underlying regulations Of CCl4-perturbed metabolic pathways were discussed according to the identified metabolites. The present study proves the great potential of LC-MS based metabonomics in mapping metabolic response for toxicology. (C) 2008 Elsevier Ireland Ltd. All rights reserved.