NMR-based metabolic profiling and metabonomic approaches to problems in molecular toxicology.
We have reviewed the main contributions to the development of NMR-based metabonomic and metabolic profiling approaches for toxicological assessment, biomarker discovery, and studies on toxic mechanisms. The metabonomic approach, (defined as the quantitative measurement of the multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modification) was originally developed to assist interpretation in NMR-based toxicological studies. However, in recent years there has been extensive fusion with metabolomic and other metabolic profiling approaches developed in plant biology, and there is much wider coverage of the biomedical and environmental fields. Specifically, metabonomics involves the use of spectroscopic techniques with statistical and mathematical tools to elucidate dominant patterns and trends directly correlated with time-related metabolic fluctuations within spectral data sets usually derived from biofluids or tissue samples. Temporal multivariate metabolic signatures can be used to discover biomarkers of toxic effect, as general toxicity screening aids, or to provide novel mechanistic information. This approach is complementary to proteomics and genomics and is applicable to a wide range of problems, including disease diagnosis, evaluation of xenobiotic toxicity, functional genomics, and nutritional studies. The use of biological fluids as a source of whole organism metabolic information enhances the use of this approach in minimally invasive longitudinal studies.
Coen
Muireann
M
Department of Biomolecular Medicine, Surgery, Oncology, Reproductive Biology and Anesthetics Division, Faculty of Medicine, Imperial College London, London, UK.
Holmes
Elaine
E
Lindon
John C
JC
Nicholson
Jeremy K
JK
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D023281:Genomics; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000295:instrumentation*; D013058:Mass Spectrometry; D008660:Metabolism; D017720:Molecular Epidemiology; D052616:Solid Phase Extraction; D014116:Toxicology / Q000639:trends*
D015415:Biomarkers