A 1H NMR-based metabonomic study of urine and plasma samples obtained from healthy human subjects

被引:220
作者
Lenz, EM
Bright, J
Wilson, ID
Morgan, SR
Nash, AFP
机构
[1] AstraZeneca Pharmaceut, DMPK, Macclesfield SK10 4TG, Cheshire, England
[2] AstraZeneca Pharmaceut, Dept Enabling Sci & Technol, Macclesfield SK10 4TG, Cheshire, England
[3] AstraZeneca Pharmaceut, Dept Expt Med, Macclesfield SK10 4TG, Cheshire, England
关键词
metabonomics; H-1 NMR spectroscopy; diurnal variation; metabolic profiling; human subjects;
D O I
10.1016/S0731-7085(03)00410-2
中图分类号
O65 [分析化学];
学科分类号
070302 ; 081704 ;
摘要
The aim of the study was to assess the feasibility of metabonomics in clinical studies. A H-1 nuclear magnetic resonance (NMR)-based metabonomic analysis was performed on plasma and urine samples obtained from a group of 12 healthy male subjects on two separate study days 14 days apart. The subjects were fed a standard diet and plasma and urine samples were obtained on both days. The 1H NMR spectra obtained for urine and plasma samples were analysed using principal components analysis (PCA) in order to generate metabonomic data. In plasma there was relatively little variability between subjects and study days. In the case of endogenous urinary metabolite profiles there was considerable inter-subject variability, but less intra-subject variation. In all subjects diurnal variation was seen with urine samples. This suggests the possibility to collect consistent metabonomics data in clinical studies. (C) 2003 Elsevier B.V. All rights reserved.
引用
收藏
页码:1103 / 1115
页数:13
相关论文
共 11 条
[1]   Investigations into biochemical changes due to diurnal variation and estrus cycle in female rats using high-resolution 1H NMR spectroscopy of urine and pattern recognition [J].
Bollard, ME ;
Holmes, E ;
Lindon, JC ;
Mitchell, SC ;
Branstetter, D ;
Zhang, W ;
Nicholson, JK .
ANALYTICAL BIOCHEMISTRY, 2001, 295 (02) :194-202
[2]  
Brindle JT, 2002, NAT MED, V8, P1439, DOI 10.1038/nm802
[3]   Optimisation of collection, storage and preparation of rat plasma for 1H NMR spectroscopic analysis in toxicology studies to determine inherent variation in biochemical profiles [J].
Deprez, S ;
Sweatman, BC ;
Connor, SC ;
Haselden, JN ;
Waterfield, CJ .
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, 2002, 30 (04) :1297-1310
[4]   Directly coupled high-performance liquid chromatography and nuclear magnetic resonance spectroscopic with chemometric studies on metabolic variation in Sprague-Dawley rats [J].
Gavaghan, CL ;
Nicholson, JK ;
Connor, SC ;
Wilson, ID ;
Wright, B ;
Holmes, E .
ANALYTICAL BIOCHEMISTRY, 2001, 291 (02) :245-252
[5]   Physiological variation in metabolic phenotyping and functional genomic studies: use of orthogonal signal correction and PLS-DA [J].
Gavaghan, CL ;
Wilson, ID ;
Nicholson, JK .
FEBS LETTERS, 2002, 530 (1-3) :191-196
[6]   An NMR-based metabonomic approach to investigate the biochemical consequences of genetic strain differences:: application to the C57BL10J and Alpk:ApfCD mouse [J].
Gavaghan, CL ;
Holmes, E ;
Lenz, E ;
Wilson, ID ;
Nicholson, JK .
FEBS LETTERS, 2000, 484 (03) :169-174
[7]   Pattern recognition methods and applications in biomedical magnetic resonance [J].
Lindon, JC ;
Holmes, E ;
Nicholson, JK .
PROGRESS IN NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY, 2001, 39 (01) :1-40
[8]   Contemporary issues in toxicology - The role of metabonomics in toxicology and its evaluation by the COMET project [J].
Lindon, JC ;
Nicholson, JK ;
Holmes, E ;
Antti, H ;
Bollard, ME ;
Keun, H ;
Beckonert, O ;
Ebbels, TM ;
Reilly, MD ;
Robertson, D ;
Stevens, GJ ;
Luke, P ;
Breau, AP ;
Cantor, GH ;
Bible, RH ;
Niederhauser, U ;
Senn, H ;
Schlotterbeck, G ;
Sidelmann, UG ;
Laursen, SM ;
Tymiak, A ;
Car, BD ;
Lehman-McKeeman, L ;
Colet, JM ;
Loukaci, A ;
Thomas, C .
TOXICOLOGY AND APPLIED PHARMACOLOGY, 2003, 187 (03) :137-146
[9]   'Metabonomics': understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data [J].
Nicholson, JK ;
Lindon, JC ;
Holmes, E .
XENOBIOTICA, 1999, 29 (11) :1181-1189
[10]   Metabonomics: a platform for studying drug toxicity and gene function [J].
Nicholson, JK ;
Connelly, J ;
Lindon, JC ;
Holmes, E .
NATURE REVIEWS DRUG DISCOVERY, 2002, 1 (02) :153-161