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Identification of disease- and nutrient-related metabolic fingerprints in osteoarthritic guinea pigs

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Author: Lamers, R.-J.A.N. · Groot, J. de · Spies-Faber, E.J. · Jellema, R.H. · Kraus, V.B. · Verzijl, N. · Koppele, J.M. te · Spijksma, G.K. · Vogels, J.T.W.E. · Greef, J. van der · Nesselrooij, J.H.J. van
Type:article
Date:2003
Source:Journal of Nutrition, 6, 133, 1776-1780
Identifier: 237136
Keywords: Biology · Analytical research · Biomedical research · 1H NMR spectroscopy · Metabolic fingerprinting · Multivariate data analysis · Osteoarthritis · Vitamin C · ascorbic acid · biological marker · purine · animal experiment · animal model · article · controlled study · data analysis · dietary intake · disease marker · energy metabolism · guinea pig · inbred strain · male · metabolic fingerprint · metabolism · metabolite · multivariate analysis · nonhuman · nutrient · nutrition · osteoarthritis · pathophysiology · proton nuclear magnetic resonance · purine metabolism · strain difference · urinalysis · vitamin intake · Animal Nutrition Physiology · Animals · Ascorbic Acid · Diet · Dose-Response Relationship, Drug · Energy Metabolism · Guinea Pigs · Magnetic Resonance Spectroscopy · Male · Multivariate Analysis · Osteoarthritis · Peptide Mapping · Purines · Treatment Outcome · Animalia · Cavia · Cavia porcellus · Sus scrofa

Abstract

Osteoarthritis (OA), one of the most common diseases among the elderly, is characterized by the progressive destruction of joint tissues. Its etiology is largely unclear and no effective disease-modifying treatment is currently available. Metabolic fingerprinting provides a novel tool for the identification of biomarkers. A metabolic fingerprint consists of a typical combination of metabolites in a biological fluid and is identified by a combination of 1H NMR spectroscopy and multivariate data analysis (MVDA). The current feasibility study was aimed at identifying a metabolic fingerprint for OA and applying this in a nutritional intervention study. Urine samples were collected from osteoarthritic male Hartley guinea pigs (n = 44) at 10 and 12 mo of age, treated from 4 mo onward with variable vitamin C doses (2.5-3, 30 and 150 mg/d) and from healthy male Strain 13 guinea pigs (n = 8) at 12 mo of age, treated with 30 mg vitamin C/d. NMR measurements were performed on all urine samples. Subsequently, MVDA was carried out on the data obtained using NMR. An NMR fingerprint was identified that reflected the osteoarthritic changes in guinea pigs. The metabolites that comprised the fingerprint indicate that energy and purine metabolism are of major importance in OA. Metabolic fingerprinting also allowed detection of differences in OA-specific metabolites induced by different dietary vitamin C intakes. This study demonstrates the feasibility of metabolic fingerprinting to identify disease-specific profiles of urinary metabolites. NMR fingerprinting is a promising means of identifying new disease markers and of gaining fresh insights into the pathophysiology of disease.