Increase of uric acid and purine compounds in biological fluids of multiple sclerosis patients

被引:91
作者
Amorini, Angela M. [2 ]
Petzold, Axel [3 ]
Tavazzi, Barbara [2 ]
Eikelenboom, Judith [4 ]
Keir, Geoffrey [3 ]
Belli, Antonio [5 ]
Giovannoni, Gavin [6 ]
Di Preto, Valentina [2 ]
Polman, Chris [4 ]
D'Urso, Serafina [1 ]
Vagnozzi, Roberto [7 ]
Uitdehaag, Bernard [4 ]
Lazzarino, Giuseppe [1 ]
机构
[1] Univ Catania, Biochem Lab, Dept Chem Sci, I-95125 Catania, Italy
[2] Catholic Univ Rome Sacro Cuore, Inst Biochem & Clin Biochem, Rome, Italy
[3] UCL, Inst Neurol, Neuroimmunol & CSF Unit, Dept Neuroinflammat, London, England
[4] Univ Amsterdam, Dept Neurol, VU Med Ctr, Amsterdam, Netherlands
[5] Univ Southampton, Div Clin Neurosci, Southampton, Hants, England
[6] Royal London Hosp, Dept Neurol, London E1 1BB, England
[7] Univ Roma Tor Vergata, Dept Neurosci, Rome, Italy
关键词
Multiple sclerosis; Uric acid; Purine compounds; Cerebrospinal fluid; Serum; HPLC; Energy metabolism; Oxidative stress; Nitrosative stress; TRAUMATIC BRAIN-INJURY; CEREBROSPINAL-FLUID; MITOCHONDRIAL DYSFUNCTION; OXIDATIVE STRESS; LIPID-PEROXIDATION; NITROSATIVE STRESS; CYCLOSPORINE-A; ENERGY-STATE; HYPOXANTHINE; XANTHINE;
D O I
10.1016/j.clinbiochem.2009.03.020
中图分类号
R446 [实验室诊断]; R-33 [实验医学、医学实验];
学科分类号
1001 ;
摘要
Objectives: In this study, the concentrations of uric acid, purine profile and creatinine in samples of cerebrospinal fluid and serum of multiple sclerosis (MS) patients were measured by HPLC and compared with corresponding values recorded in patients Without MS (cerebrospinal fluid) and healthy subjects (serum). Design and methods: All samples were deproteinized with ultrafiltration (which ensures minimal sample manipulation and efficient protein removal) and then assayed for the synchronous HPLC separation of uric acid, hypoxanthine, xanthine, inosine, adenosine, guanosine and creatinine. Results: The values of all compounds assayed were significantly higher in both biological fluids of MS patients with respect to values measured in controls. In particular, serum hypoxanthine, xanthine, uric acid and sum of oxypurines were, respectively, 3.17, 3.11, 1.23 and 1.27-fold higher in these patients than corresponding values recorded in controls (p < 0.001). Conclusions: Differently from what previously reported, we here demonstrate that all purine compounds, including uric acid, are elevated in biological fluids of MS patients. Reinforced by the trend observed for creatinine, this corroborates the notion of sustained purine catabolism, possibly due to imbalance in ATP homeostasis, under these pathological conditions. These results cast doubt oil the hypothesis that uric acid is depleted in MS because of increased oxidative stress, rather suggesting that this disease causes a generalized increase in purine catabolism. As observed in other pathological states, uric acid, purine compounds and creatinine, can be considered markers of metabolic energy imbalance rather than of reactive oxygen species, even in MS. (c) 2009 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.
引用
收藏
页码:1001 / 1006
页数:6
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