Metabolic Profiling as a Tool for Understanding Mechanisms of Toxicity
Metabolic Profiling as a Tool for Understanding Mechanisms of Toxicity
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DOI：
10.1177/0192623307310947
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发表时间：
2008-01-01
影响因子：
1.5
通讯作者：
Haselden, John N.
中科院分区：
文献类型：
--
作者：
Clarke, Christopher J.;Haselden, John N.
代谢谱（代谢组学/代谢组学）是对生物系统中低分子量代谢物及其中间体的补体的测量，反映了对基因修饰和生理、病理生理和/或发育刺激的动态反应。生物样本（通常是尿液、血清或生物组织提取物）的内源性代谢物谱的测量和解释为研究外部刺激（例如药物治疗）引起的变化或增强我们对亚种群内在生物变异的认识提供了许多机会。本文将重点介绍代谢谱分析的基本原理以及这些工具（核磁共振[NMR]，液相色谱-质谱分析[LC-MS]）如何在毒理学和病理学中应用。在研究临床前药物开发问题时，代谢谱分析可以补充传统方法和其他“组学”技术。案例研究将说明代谢谱在提高我们对磷脂病和过氧化物酶体增殖的理解方面的价值。一个关键的信息是，代谢分析提供了巨大的潜力，以突出生物标志物和机制，支持临床前药物开发的毒理学和病理学研究。
Metabolic profiling (metabolomics/metabonomics) is the measurement in biological systems of the complement of low-molecular-weight metabolites and their intermediates that reflects the dynamic response to genetic modification and physiological, pathophysiological, and/or developmental stimuli. The measurement and interpretation of the endogenous metabolite profile from a biological sample (typically urine, serum, or biological tissue extract) have provided many opportunities to investigate the changes induced by external stimuli (e. g., drug treatment) or enhance our knowledge of inherent biological variation within subpopulations. This article will focus on the basic principles of metabolic profiling and how the tools (nuclear magnetic resonance [NMR], liquid chromatography-mass spectrometry [LC-MS]) can be applied in toxicology and pathology. Metabolic profiling can complement conventional methodologies and other "omics" technologies in investigating preclinical drug development issues. Case studies will illustrate the value of metabolic profiling in improving our understanding of phospholipidosis and peroxisome proliferation. A key message will be that metabolic profiling offers huge potential to highlight biomarkers and mechanisms in support of toxicology and pathology investigations in preclinical drug development.