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

Bollard, Mary E.; Holmes, Elaine; Lindon, John C.; Mitchell, Siân; Branstetter, Daniel; Zhang, W.; Nicholson, Jeremy K.

doi:10.1006/abio.2001.5211

Cited by 176 publications

(128 citation statements)

References 24 publications

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“…27,33 However, many endogenous metabolites, such as taurine, fluctuate in concentration as a result of normal physiological variation. 5 Therefore, its significance is measured by concomitant changes in other metabolites, for instance, elevated creatine 34,35 or a decrease in hippurate. 27,33 The combined increases in taurine and creatine concentrations have been associated with reduced liver function after treatment of rats with carbon tetrachloride, thioacetamide and allyl alcohol.…”

Section: Nmr Based Metabonomicsmentioning

confidence: 99%

“…46 In a previous study into physiological variation in female SD rats, urine from a group of 10 animals was sampled over a 10 day period. 5 From PCA of the data, the scores from the first two PCs were tabulated and the mean values and standard deviation ellipses for each rat mapped using the mean integral values of urinary spectral data as input variables (Fig. 8).…”

Section: Metabonomic Studies Of Physiological Variationmentioning

confidence: 99%

“…3 Furthermore, NMR spectroscopy together with pattern recognition (PR) techniques has been used extensively for the investigation of the inherent metabolic variability in control populations of experimental animals. [4][5][6][7] Metabonomics addresses complete biological systems by studying metabolic profiles, mainly in biofluids, which gives a window on whole systems biochemistry and thus promises to provide crucial information on drug toxicity, disease processes and gene function. 8 However, in order to be confident of perturbed metabolic profiles in such cases, it is necessary to characterize the boundaries of metabolic 'normality'.…”

Section: Introductionmentioning

confidence: 99%

“…Variation between animals or between different strains, for instance, is generally much less than the variation in response due to exposure to different toxicants. 5,10 An 1 H NMR spectrum of a biofluid or tissue is extremely complex, consisting of thousands of wellresolved signals, the intensities of which relate to the concentration of these metabolites in the sample. Therefore, the NMR spectrum enables the simultaneous identification and monitoring of a wide range of low molecular weight endogenous metabolites, thus providing a biochemical fingerprint of an organism.…”

Section: Introductionmentioning

confidence: 99%

“…11 It is now well established that this profile can be changed by a disease or toxic process, [10][11][12][13][14] or by an effect on the nutritional state or lifestyle of the animal. [4][5][6][7] The application of data-rich analytical chemistry technology to study the multi-component metabolic composition of biofluids, cells and tissues and from studies utilizing PR, expert systems and related bio-informatic tools to interpret and classify the complex data sets is known as 'metabonomics'. 15,16 Similarly the term 'metabolomics' was originally used to describe the metabolome or metabolic composition of a cell.…”

Section: Introductionmentioning

confidence: 99%

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NMR-based metabonomic approaches for evaluating physiological influences on biofluid composition

et al. 2004

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Strategies such as genomics, proteomics and metabonomics are being applied with increasing frequency in the pharmaceutical industry. For each of these approaches, toxicological response can be measured by terms of deviation from control or baseline status. However, in order to accurately define drug-induced response, it is necessary to characterize the normal degree of physiological variation in the absence of stimuli. Here, 1 H NMR spectroscopic-based analyses of the metabolic composition of urine in experimental animals under various normal physiological conditions are reviewed. In particular, the effects of inter-animal and diurnal variation, gender, age, diet, species, strain, hormonal status and stress on the biochemical composition of urine are explored. Pattern recognition methods facilitate the comparison of urine NMR spectra over a given time-course, enabling the establishment of changes in profile and highlighting the dynamic metabolic status of an organism. Thus metabonomic approaches based on information-rich spectroscopic data sets can be used to evaluate normal physiological variation and for investigation of drug safety issues.

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Section: Nmr Based Metabonomicsmentioning

confidence: 99%

Section: Metabonomic Studies Of Physiological Variationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

NMR-based metabonomic approaches for evaluating physiological influences on biofluid composition

et al. 2004

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A Metabolomic Perspective of Small Molecule Toxicity

Patterson

Idle

2009

General, Applied and Systems Toxicology

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Recent advances in small molecule profiling, including ultraperformance liquid chromatography and time‐of‐flight mass spectrometry, have given unprecedented views of the metabolic response to toxic stimuli. Metabolomics, the process of measuring the concentration changes in metabolites of biofluids such as urine, serum, sweat or saliva or that of intact cells, tissues or single‐celled organisms, is the missing piece of the omics puzzle (genomics, transcriptomics, proteomics) necessary for providing a holistic view (DNA, RNA, protein and metabolites) of the biological response to a toxicant. Furthermore, metabolomics is an essential addition to any toxicity biomarker‐screening programme, as evidenced by its strong foothold in both pharmaceutical and academic settings. Here we discuss metabolomic science with respect to its past and future contributions to the field of toxicology and describe blueprints necessary for conducting a well‐designed and robust metabolomics experiment from sample collection to data acquisition and analysis. Metabolomics holds great promise as a tool for advancing the field of toxicology by uncovering novel biomarkers of toxic responses and by significantly improving xenobiotic metabolite identification.

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