Xenobiotic exposure, especially high-dose or repeated exposure of xenobiotics, can elicit detrimental effects on biological systems through diverse mechanisms. Changes in metabolic systems, including formation of reactive metabolites and disruption of endogenous metabolism, are not only the common consequences of toxic xenobiotic exposure, but in many cases are the major causes behind development of xenobiotic-induced toxicities (XIT). Therefore, examining the metabolic events associated with XIT generates mechanistic insights into the initiation and progression of XIT, and provides guidance for prevention and treatment. Traditional bioanalytical platforms that target only a few suspected metabolites are capable of validating the expected outcomes of xenobiotic exposure. However, these approaches lack the capacity to define global changes and to identify unexpected events in the metabolic system. Recent developments in high-throughput metabolomics have dramatically expanded the scope and potential of metabolite analysis. Among all analytical techniques adopted for metabolomics, liquid chromatography-mass spectrometry (LC-MS) has been most widely used for metabolomic investigations of XIT due to its versatility and sensitivity in metabolite analysis. In this review, technical platform of LC-MS-based metabolomics, including experimental model, sample preparation, instrumentation, and data analysis, are discussed. Applications of LC-MS-based metabolomics in exploratory and hypothesis-driven investigations of XIT are illustrated by case studies of xenobiotic metabolism and endogenous metabolism associated with xenobiotic exposure.
|Original language||English (US)|
|Journal||Computational and Structural Biotechnology Journal|
|State||Published - Jan 2013|
Bibliographical noteFunding Information:
Research projects in Dr. Chi Chen's lab were supported in part by an Agricultural Experiment Station project MIN-18-082 from the United States Department of Agriculture (USDA), and by R21-DA027469 grant to Dr. Chi Chen from the National Institutes on Drug Abuse (NIDA) , National Institutes of Health (NIH). We are very grateful to Dr. Brian A. Crooker for editing and proofreading this manuscript. We thank all the members in Dr. Chi Chen's lab for their help in preparing this manuscript.
- Xenobiotic-Induced Toxicity