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      Low uric acid levels in patients with Parkinson's disease: evidence from meta-analysis

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      BMJ Open
      BMJ Publishing Group

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          Abstract

          Objective

          The association between Parkinson's disease (PD) and uric acid levels has gained intensive interest in recent years. We applied meta-analysis to investigate serum uric acid levels in patients with PD in comparison with healthy controls.

          Design

          We searched three electronic databases and reference lists up to January 2013. Two collaborators reviewed all the articles and data disagreement was resolved through discussion. Six studies met the eligibility criteria and were included in the meta-analysis of uric acid levels in patients with PD in comparison with controls.

          Participants

          1217 patients with PD and 1276 matched healthy controls.

          Results

          The meta-analysis results showed that patients with PD had lower levels of uric acid than healthy controls (summary standardised mean difference (SMD)=−0.52, 95% CI (−0.72 to −0.31)). Further gender subgroup analysis (summary SMD=−0.56, 95% CI (−0.72 to −0.41) for women; summary SMD=−0.62, 95% CI (−0.94 to −0.31) for men) indicated lower uric acid levels in patients with PD than healthy controls in women and men.

          Conclusions

          It was found that patients with PD had lower serum levels of uric acid than healthy controls and this association was more significant in men than in women. More efforts are encouraged to explore the prognostic and therapeutic implications for PD of the present findings.

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          Most cited references30

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          Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis.

          During primate evolution, a major factor in lengthening life-span and decreasing age-specific cancer rates may have been improved protective mechanisms against oxygen radicals. We propose that one of these protective systems is plasma uric acid, the level of which increased markedly during primate evolution as a consequence of a series of mutations. Uric acid is a powerful antioxidant and is a scavenger of singlet oxygen and radicals. We show that, at physiological concentrations, urate reduces the oxo-heme oxidant formed by peroxide reaction with hemoglobin, protects erythrocyte ghosts against lipid peroxidation, and protects erythrocytes from peroxidative damage leading to lysis. Urate is about as effective an antioxidant as ascorbate in these experiments. Urate is much more easily oxidized than deoxynucleosides by singlet oxygen and is destroyed by hydroxyl radicals at a comparable rate. The plasma urate levels in humans (about 300 microM) is considerably higher than the ascorbate level, making it one of the major antioxidants in humans. Previous work on urate reported in the literature supports our experiments and interpretations, although the findings were not discussed in a physiological context.
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            Parkinson's disease. First of two parts.

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              Oxidative stress and the pathogenesis of Parkinson's disease.

              Current concepts of the pathogenesis of Parkinson's disease (PD) center on the formation of reactive oxygen species and the onset of oxidative stress leading to oxidative damage to substantia nigra pars compacta. Extensive postmortem studies have provided evidence to support the involvement of oxidative stress in the pathogenesis of PD; in particular, these include alterations in brain iron content, impaired mitochondrial function, alterations in the antioxidant protective systems (most notably superoxide dismutase [SOD] and reduced glutathione [GSH]), and evidence of oxidative damage to lipids, proteins, and DNA. Iron can induce oxidative stress, and intranigral injections have been shown to induce a model of progressive parkinsonism. A loss of GSH is associated with incidental Lewy body disease and may represent the earliest biochemical marker of nigral cell loss. GSH depletion alone may not result in damage to nigral neurons but may increase susceptibility to subsequent toxic or free radical exposure. The nature of the free radical species responsible for cell death in PD remains unknown, but there is evidence of involvement of hydroxyl radical (OH.), peroxynitrite, and nitric oxide. Indeed, OH. and peroxynitrite formation may be critically dependent on nitric oxide formation. Central to many of the processes involved in oxidative stress and oxidative damage in PD are the actions of monoamine oxidase-B (MAO-B). MAO-B is essential for the activation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine to 1-methyl-4-phenylpyridinium ion, for a component of the enzymatic conversion of dopamine to hydrogen peroxide (H2O2), and for the activation of other potential toxins such as isoquinolines and beta-carbolines. Thus, the inhibition of MAO-B by drugs such as selegiline may protect against activation of some toxins and free radicals formed from the MAO-B oxidation of dopamine. In addition, selegiline may act through a mechanism unrelated to MAO-B to increase neurotrophic factor activity and upregulate molecules such as glutathione, SOD, catalase, and BCL-2 protein, which protect against oxidant stress and apoptosis. Consequently, selegiline may be advantageous in the long-term treatment of PD.
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                Author and article information

                Journal
                BMJ Open
                BMJ Open
                bmjopen
                bmjopen
                BMJ Open
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                2044-6055
                2013
                16 November 2013
                : 3
                : 11
                : e003620
                Affiliations
                Shandong Provincial Research Center for Bioinformatic Engineering and Technique, Shandong University of Technology , Zibo, People's Republic of China
                Author notes
                [Correspondence to ] Dr Hong-Fang Ji; jhf@ 123456sdut.edu.cn
                Article
                bmjopen-2013-003620
                10.1136/bmjopen-2013-003620
                3840343
                24247326
                dc99cb56-e32c-4b27-bb7a-ced374d08c82
                Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions

                This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/

                History
                : 20 July 2013
                : 17 October 2013
                : 18 October 2013
                Categories
                Neurology
                Research
                1506
                1713
                1692

                Medicine
                Medicine

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