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Metabonomics represents a holistic, hypothesis-free, approach to the study of metabolic responses to various stimuli through powerful data acquisition and advanced data processing techniques. This approach aims to the highthroughput analysis of the metabolic profiles of biofluids, tissues, extracts etc taking advantage of the degree of inherent biochemical similarities between samples.
NMR spectroscopy and/or MS have been utilized as main analytical platforms in Metabonomics studies. The application of NMR spectroscopy to biological materials allows the simultaneous detection, identification, and quantitation of a variety of low-molecular-weight metabolites from a range of intermediate metabolic pathways. This is possible in combination with the newly emerging methods for automated data reduction and pattern recognition techniques (multivariate chemometric analysis) leading to the efficient exploitation of complex NMR spectral profiles.

NMR-based metabonomics presents a holistic picture of the metabolites’ alterations in the organism that can revolutionize systems biology. It combines data obtained from the spectroscopic and multivariate statistical analyses to cluster the samples according to their common spectroscopic/metabolic characteristics. Initially applied in experimental animal models of toxicity, the metabonomic approach has been used as a powerful tool in the fields of drug toxicology. The last decade is expanded in the study of endogenous metabolites alterations in human biofluids (e.g. plasma, serum, urine), in order to develop models for diagnosis of major diseases like coronary heart disease and cancer, providing an insight into the mechanisms of pathophysiological alterations and the determination of novel disease biomarkers.

Selected Publications

Zira, A., Kostidis, S., Theocharis, S., Sigala, F., Engelsen, S.B., Andreadou, I., Mikros, E. 1H NMR-based metabonomics approach in a rat model of acute liver injury and regeneration induced by CCl4 administration (2012) Toxicology, 303, pp. 115-124. Article in Press.
DOI: 10.1016/j.tox.2012.10.015

Andreadou, I., Iliodromitis, E.K., Souridis, V., Prokovas, E., Kostidis, S., Zoga, A., Dagres, N., Tsantili-Kakoulidou, A., Kremastinos, D.Th., Mikros, E., Anastasiou-Nana, M. Investigating the effect of antioxidant treatment on the protective effect of preconditioning in anesthetized rabbits (2011) Journal of Cardiovascular Pharmacology, 58 (6), pp. 609-616.
DOI: 10.1097/FJC.0b013e31822fc783

Pechlivanis, A., Kostidis, S., Saraslanidis, P., Petridou, A., Tsalis, G., Mougios, V., Gika, H.G., Mikros, E., Theodoridis, G.A. 1H NMR-based metabonomic investigation of the effect of two different exercise sessions on the metabolic fingerprint of human urine (2010) Journal of Proteome Research, 9 (12), pp. 6405-6416.
DOI: 10.1021/pr100684t

Zira, A.N., Theocharis, S.E., Mitropoulos, D., Migdalis, V., Mikros, E. 1H NMR metabonomic analysis in renal cell carcinoma: A possible diagnostic tool (2010) Journal of Proteome Research, 9 (8), pp. 4038-4044.
DOI: 10.1021/pr100226m

Anastasiadi, M., Zira, A., Magiatis, P., Haroutounian, S.A., Skaltsounis, A.L., Mikros, E. H NMR-based metabonomics for the classification of Greek wines according to variety, region, and vintage. comparison with HPLC data (2009) Journal of Agricultural and Food Chemistry, 57 (23), pp. 11067-11074.
DOI: 10.1021/jf902137e

Andreadou, I., Papaefthimiou, M., Zira, A., Constantinou, M., Sigala, F., Skaltsounis, A.-L., Tsantili-Kakoulidou, A., Iliodromitis, E.K., Kremastinos, D.T., Mikros, E. Metabonomic identification of novel biomarkers in doxorubicin cardiotoxicity and protective effect of the natural antioxidant oleuropein (2009) NMR in Biomedicine, 22 (6), pp. 585-592.
DOI: 10.1002/nbm.1370

Benaki, D., Stathopoulou, K., Leondiadis, L., Ferderigos, N., Pelecanoua, M., Mikros, E. Detection of interactions of the β-amyloid peptide with small molecules employing transferred NOEs (2009) Journal of Peptide Science, 15 (6), pp. 435-441.
DOI: 10.1002/psc.1138

Zira, A., Mikros, E., Giannioti, K., Galanopoulou, P., Papalois, A., Liapic, C., Theocharis, S. Acute liver acetaminophen toxicity in rabbits and the use of antidotes: A metabonomic approach in serum (2009) Journal of Applied Toxicology, 29 (5), pp. 395-402.
DOI: 10.1002/jat.1425

Constantinou, M.A., Tsantili-Kakoulidou, A., Andreadou, I., Iliodromitis, E.K., Kremastinos, D.Th., Mikros, E. Application of NMR-based metabonomics in the investigation of myocardial ischemia-reperfusion, ischemic preconditioning and antioxidant intervention in rabbits (2007) European Journal of Pharmaceutical Sciences, 30 (3-4), pp. 303-314.
DOI: 10.1016/j.ejps.2006.11.016

Constantinou, M.A., Vertzoni, M., Reppas, C., Tsantili-Kakoulidou, A., Mikros, E. 1H NMR monitoring of the canine metabolic profile after oral administration of xenobiotics using multivariate statistics (2007) Molecular Pharmaceutics, 4 (2), pp. 258-268.
DOI: 10.1021/mp060069z

Constantinou, M.A., Theocharis, S.E., Mikros, E. Application of metabonomics on an experimental model of fibrosis and cirrhosis induced by thioacetamide in rats (2007) Toxicology and Applied Pharmacology, 218 (1), pp. 11-19.
DOI: 10.1016/j.taap.2006.10.007

Constantinou, M.A., Papakonstantinou, E., Spraul, M., Sevastiadou, S., Costalos, C., Koupparis, M.A., Shulpis, K., Tsantili-Kakoulidou, A., Mikros, E. 1H NMR-based metabonomics for the diagnosis of inborn errors of metabolism in urine (2005) Analytica Chimica Acta, 542 (2), pp. 169-177.
DOI: 10.1016/j.aca.2005.03.059

Constantinou, M.A., Papakonstantinou, E., Benaki, D., Spraul, M., Shulpis, K., Koupparis, M.A., Mikros, E. Application of nuclear magnetic resonance spectroscopy combined with principal component analysis in detecting inborn errors of metabolism using blood spots: A metabonomic approach (2004) Analytica Chimica Acta, 511 (2), pp. 303-312.
DOI: 10.1016/j.aca.2004.02.012