Serum UPLC-MS/MS metabolic profiling in an experimental model for acute-liver injury reveals potential biomarkers for hepatotoxicity.
Serum UPLC-MS/MS metabolic profiling in an experimental model for acute-liver injury reveals potential biomarkers for hepatotoxicity.
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DOI：
10.1007/s11306-011-0329-9
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发表时间：
2012
期刊：
影响因子：
3.6
通讯作者：
Falcon-Perez, Juan M.
中科院分区：
文献类型：
--
作者：
Gonzalez, Esperanza;van Liempd, Sebastiaan;Conde-Vancells, Javier;Gutierrez-de Juan, Virginia;Perez-Cormenzana, Miriam;Mayo, Rebeca;Berisa, Agustin;Alonso, Cristina;Marquez, Cesar A.;Barr, Jonathan;Lu, Shelly C.;Mato, Jose M.;Falcon-Perez, Juan M.
关键词：
临床诊断和制药行业的一个关键兴趣是拥有一个非侵入性生物标志物的库，以单独或组合能够推断或预测病理条件或药物引起的肝损伤的程度。代谢组学是对全球代谢物的综合研究，由于最近的技术进步，代谢组学已经成为发现生物标志物的高度敏感和强大的工具。采用超高效液相色谱/飞行时间串联质谱（UPLC/TOF MS/MS）为基础的代谢组学方法，研究半乳糖胺处理的大鼠血清，以寻找急性肝损伤的潜在生物标志物。通过测定血清转氨酶活性和原位肝组织学病变来量化肝损伤。主成分分析结合相关系数分析用于生物标志物的选择和鉴定。根据这些数据，包括葡萄糖，氨基酸和膜脂质在内的几种代谢物的血清水平显着改变，其中一些显示出与肝脏组织学检查确定的肝损伤程度高度相关。总之，本研究支持在实验动物模型中基于UPLC-MS/MS的血清代谢组学可能是寻找药物或疾病诱导的肝损伤的生物标志物的有力方法。
A key interest in clinical diagnosis and pharmaceutical industry is to have a repertoire of noninvasive biomarkers to—individually or in combination—be able to infer or predict the degree of liver injury caused by pathological conditions or drugs. Metabolomics—a comprehensive study of global metabolites—has become a highly sensitive and powerful tool for biomarker discovery thanks to recent technological advances. An ultra-performance liquid chromatography/time-of-flight tandem mass spectrometry (UPLC/TOF MS/MS)-based metabolomics approach was employed to investigate sera from galactosamine-treated rats to find potential biomarkers for acute liver injury. Hepatic damage was quantified by determining serum transaminase activity and in situ liver histological lesions. Principal component analysis in combination with coefficient of correlation analysis was used for biomarker selection and identification. According to the data, serum levels of several metabolites including glucose, amino acids, and membrane lipids were significantly modified, some of them showing a high correlation with the degree of liver damage determined by histological examination of the livers. In conclusion, this study supports that UPLC-MS/MS based serum metabolomics in experimental animal models could be a powerful approach to search for biomarkers for drug- or disease-induced liver injury.
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