Xenobiotic Metabolomics: Major Impact on the Metabolome

被引:189
作者
Johnson, Caroline H. [1 ]
Patterson, Andrew D. [2 ,3 ]
Idle, Jeffrey R. [4 ]
Gonzalez, Frank J. [1 ]
机构
[1] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA
[2] Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA
[3] Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA
[4] Univ Bern, Dept Clin Res, Hepatol Res Grp, CH-3010 Bern, Switzerland
来源
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 52 | 2012年 / 52卷
关键词
pharmacometabolomics; gut microflora; interindividual variation; metabotype; UPLC; mass spectrometry; PREGNANE-X-RECEPTOR; SPECTROMETRY-BASED METABOLOMICS; QTOFMS-BASED METABOLOMICS; FLIGHT MASS-SPECTROMETRY; GAMMA-IRRADIATED RATS; HUMAN DRUG-METABOLISM; ST-JOHNS-WORT; MOUSE MODEL; INTESTINAL MICROBIOTA; GAS-CHROMATOGRAPHY;
D O I
10.1146/annurev-pharmtox-010611-134748
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Xenobiotics are encountered by humans on a daily basis and include drugs, environmental pollutants, cosmetics, and even components of the diet. These chemicals undergo metabolism and detoxication to produce numerous metabolites, some of which have the potential to cause unintended effects such as toxicity. They can also block the action of enzymes or receptors used for endogenous metabolism or affect the efficacy and/or bioavailability of a coadministered drug. Therefore, it is essential to determine the full metabolic effects that these chemicals have on the body. Metabolomics, the comprehensive analysis of small molecules in a biofluid, can reveal biologically relevant perturbations that result from xenobiotic exposure. This review discusses the impact that genetic, environmental, and gut microflora variation has on the metabolome, and how these variables may interact, positively and negatively, with xenobiotic metabolism.
引用
收藏
页码:37 / 56
页数:20
相关论文
共 91 条
[81]   Acute renal failure secondary to fenofibrate monotherapy-induced rhabdomyolysis [J].
Tahmaz, M. ;
Kumbasar, B. ;
Ergen, K. ;
Ure, U. ;
Karatemiz, G. ;
Kazancioglu, R. .
RENAL FAILURE, 2007, 29 (07) :927-930
[82]   The Effect of Diet on the Human Gut Microbiome: A Metagenomic Analysis in Humanized Gnotobiotic Mice [J].
Turnbaugh, Peter J. ;
Ridaura, Vanessa K. ;
Faith, Jeremiah J. ;
Rey, Federico E. ;
Knight, Rob ;
Gordon, Jeffrey I. .
SCIENCE TRANSLATIONAL MEDICINE, 2009, 1 (06)
[83]   Radiation Metabolomics. 2. Dose- and Time-Dependent Urinary Excretion of Deaminated Purines and Pyrimidines after Sublethal Gamma-Radiation Exposure in Mice [J].
Tyburski, John B. ;
Patterson, Andrew D. ;
Krausz, Kristopher W. ;
Slavik, Josef ;
Fornace, Albert J., Jr. ;
Gonzalez, Frank J. ;
Idle, Jeffrey R. .
RADIATION RESEARCH, 2009, 172 (01) :42-57
[84]   Top-Down Systems Biology Modeling of Host Metabotype-Microbiome Associations in Obese Rodents [J].
Waldram, Alison ;
Holmes, Elaine ;
Wang, Yulan ;
Rantalainen, Mattias ;
Wilson, Ian D. ;
Tuohy, Kieran M. ;
McCartney, Anne L. ;
Gibson, Glenn R. ;
Nicholson, Jeremy K. .
JOURNAL OF PROTEOME RESEARCH, 2009, 8 (05) :2361-2375
[85]   Role of pregnane X receptor in control of all-trans retinoic acid (ATRA) metabolism and its potential contribution to ATRA resistance [J].
Wang, Ting ;
Ma, Xiaochao ;
Krausz, Kristopher W. ;
Idle, Jeffrey R. ;
Gonzalez, Frank J. .
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2008, 324 (02) :674-684
[86]  
WEIL A, 1988, DRUG METAB DISPOS, V16, P302
[87]  
WEIL A, 1990, DRUG METAB DISPOS, V18, P115
[88]   Untargeted Metabolomics Identifies Enterobiome Metabolites and Putative Uremic Toxins as Substrates of Organic Anion Transporter 1 (Oat1) [J].
Wikoff, William R. ;
Nagle, Megha A. ;
Kouznetsova, Valentina L. ;
Tsigelny, Igor F. ;
Nigam, Sanjay K. .
JOURNAL OF PROTEOME RESEARCH, 2011, 10 (06) :2842-2851
[89]   Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites [J].
Wikoff, William R. ;
Anfora, Andrew T. ;
Liu, Jun ;
Schultz, Peter G. ;
Lesley, Scott A. ;
Peters, Eric C. ;
Siuzdak, Gary .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (10) :3698-3703
[90]   The Role of Gut Microbiota in Drug Response [J].
Wilson, I. D. ;
Nicholson, J. K. .
CURRENT PHARMACEUTICAL DESIGN, 2009, 15 (13) :1519-1523