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

Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis,10.1073/pnas.78.11.6858,Proceed

Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis   (Citations: 484)
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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 level in humans (about 300 ..mu..M) 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.
Journal: Proceedings of The National Academy of Sciences - PNAS , vol. 78, no. 11, pp. 6858-6862, 1981
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    • ...9 On one hand, under physiological concentrations, urate (the soluble form of uric acid) is a powerful antioxidant that can scavenge superoxide, hydroxyl radicals, and singlet oxygen...

    Diana I. Jalalet al. Vascular Endothelial Function Is Not Related to Serum Uric Acid in Hea...

    • ...The incidence and prevalence of gout or hyperuricemia are rising worldwide [1, 2]. Although higher serum urate levels have been suggested to be beneficial [3], some epidemiological studies also showed an association between high uric acid (UA) levels and cardiovascular disease, hypertension, renal disease, and metabolic syndrome [4, 5]. It was well recognized that genetic factors have an important effect on the incidence of gout...

    Ming Guanet al. Association of an intronic SNP of SLC2A9 gene with serum uric acid lev...

    • ...Uric acid is a ubiquitous antioxidant in the blood [18]...

    Eswar Krishnanet al. Hyperuricemia and the risk for subclinical coronary atherosclerosis - ...

    • ...Reduction in the diameter of the lumen, the roentgenographic appearance of concentric lesions, and eccentric plaques were evaluated (the corresponding Gensini scores for reductions of 25, 50, 75, 90, and 99%, and complete occlusion were 1, 2, 4, 8, 16, and 32, respectively). For each principal vascular segment, a multiplier was assigned according to the functional significance of the myocardial area supplied by this segment: left main coronary artery × 5; proximal segment of the left anterior descending coronary artery (LAD) × 2.5; proximal segment of the circumflex artery × 2.5; midsegment of the LAD × 1.5; right coronary artery distal segment of the LAD, posterolateral artery, and obtuse marginal artery × 1, and others × 0.5.Statistical AnalysesUnless stated otherwise, all data are presented as mean ± SD. Continuous variables were checked for the normal distribution assumption using the Kolmogorov-Smirnov statistics and those that did not satisfy the criteria were log-transformed to attain normal distribution. The study group was divided into two subgroups based on the median Gensini score. Significant differences between groups were assessed using Student’s t test. χ2 was used to test differences in frequency distributions. All potential (physiologically meaningful) determinants of the Gensini score were investigated in a univariate screening procedure, using Pearson’s coefficient of correlation test. The nonparametric Spearman ρ coefficient of correlation was used to assess correlations between variables without normal distribution. Significant determinants identified from this analysis were studied in a stepwise multiple regression model using the F statistic. All variables associated with these parameters with a level of significance <0.1 were included in the tested model including Framingham risk factors and emerging risk factors. Variables were forced in the model using a stepwise procedure. p < 0.05 for the final model was considered as statistically significant. Data were analyzed using the SSPS 15.0 for Windows software (SPSS Inc., Chicago, Ill., USA).ResultsThe mean serum values for SUA, pentraxin-3 and CRP in the entire study population were 5.5 ± 1.5 mg/dl, 6.4 ± 3.4 ng/ml and 3.5 ± 2.6 mg/dl, respectively (table 1). To better characterize the categorical associations of uric acid and to identify the linear correlates of uric acid and Gensini score, we first performed simple regression analyses between these variables and all variables listed in table 1.1Table 1. Demographic and biochemical data of the patients with mild-to-moderate CKD categorized according to the median Gensini score (median Gensini score = 18)T01
      Patients in the category with a higher Gensini score had a higher SUA and pentraxin-3 levels (p < 0.001), a higher prevalence of hypertension (p = 0.001) and higher usage of ACE inhibitors and statins (p = 0.004 and p = 0.002). There were no differences for age, gender, diabetes mellitus, smoking status, LDL and HDL cholesterol, eGFR, and urinary Pr/Cr ratio of patients with Gensini score above the median and those below the median (table 1).The Gensini score values significantly correlated by univariate analysis with gender (R = –0.379, p = 0.02), uric acid level (R = 0.48, p = 0.001), pentraxin-3 (R = 0.64, p = 0.001), CRP (R = –0.29, p = 0.006), eGFR (R = –0.33, p = 0.02), proteinuria (R = 0.21, p = 0.01), and presence of hypertension (R = 0.37, p = 0.001), but not with the smoking status, presence of diabetes mellitus, and serum lipids (total, LDL and HDL cholesterol levels).To further analyze the independent contribution of uric acid to the variance of the Gensini score, we performed multiple regression models based on traditional and nontraditional risk factors impacting upon this variable. In the unadjusted analysis, uric acid and the Gensini score were positively correlated (table 2). Adjustment for the full set of Framingham risk factors did not produce any change in the correlation coefficient of the association. Adjustment for emerging risk factors (pentraxin-3 and CRP) substantially reduced the regression coefficient (model 3: β = 0.21; table 2), but did not abolish the association (p = 0.02). Further analysis showed that of the emerging risk factors added to model 3 variables, pentraxin-3 was the sole variable responsible for the attenuation of the strength of the uric acid-Gensini score association.2Table 2. Multiple regression models of the Gensini score in mild-to-moderate CKD patientsT02
      DiscussionThe main finding of this current study was that SUA levels are independently associated with CAD severity assessed by coronary angiography in patients who had mild-to-moderate CKD. A novel inflammatory marker, pentraxin-3, was also found to be associated with severity of CAD even after adjustment for traditional CAD risk factors.Uric acid had long been considered as a strong antioxidant [...

    Mehmet Kanbayet al. Uric Acid and Pentraxin-3 Levels Are Independently Associated with Cor...

    • ...Urate is the most important extracellular antioxidant [2] but has been mostly ignored in the diabetes literature...

    Robert Daniel Hoeldtkeet al. Oxidative stress and autonomic nerve function in early type 1 diabetes

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