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Uric Acid and Oxidative Stress

Part of the Oxidative Stress in Applied Basic Research and Clinical Practice book series (OXISTRESS)

Abstract

Biological effects of uric acid, generated in the human body either from food or resulting from the purine degradation pathway via xanthine oxidoreductase, are extremely pleiotropic. They are paradoxically opposing under different experimental conditions. Some of these effects are beneficial and some of them are deleterious. The key feature of uric acid is the ability to be either an antioxidant or pro-oxidant depending on a variety of factors. The complexity of the urate chemistry, including its ability to quench or form various radicals, is a crucial component of the mechanisms underlying the ability of uric acid to induce opposing biological effects. In addition, uric acid is a powerful signaling molecule that can affect intracellular signal transduction, leading to oxidant production via nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and expression of proinflammatory mediators. Beneficial antioxidant effects are manifested in the protection of endothelial cells from external oxidative stress and protection of the central nervous system from oxidative damage in several conditions. Detrimental pro-oxidative effects of uric acid are associated with the metabolic syndrome and cardiovascular and renal diseases.

Keywords

  • Xanthine oxidoreductase
  • Metabolic syndrome
  • Endothelium

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References

  1. Keilin J. The biological significance of uric acid and guanine excretion. Biol Rev Cambridge Phil Soc 1959;34:265–296

    CAS  Google Scholar 

  2. Terkeltaub RA. Gout. N Engl J Med 2003;349:1647–1655

    CAS  PubMed  CrossRef  Google Scholar 

  3. Kellogg EW, III, Fridovich I. Liposome oxidation and erythrocyte lysis by enzymically generated superoxide and hydrogen peroxide. J Biol Chem 1977;252:6721–6728

    CAS  PubMed  Google Scholar 

  4. Proctor P. Similar functions of uric acid and ascorbate in man? Nature 1970;228:868

    CAS  PubMed  CrossRef  Google Scholar 

  5. Ames BN, Cathcart R, Schwiers E, Hochstein P. Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis. Proc Natl Acad Sci U S A 1981;78:6858–6862

    CAS  PubMed  CrossRef  Google Scholar 

  6. Johnson RJ, Kang DH, Feig D, et al. Is there a pathogenetic role for uric acid in hypertension and cardiovascular and renal disease? Hypertension 2003;41:1183–1190

    CAS  PubMed  CrossRef  Google Scholar 

  7. Feig DI, Kang DH, Johnson RJ. Uric acid and cardiovascular risk. N Engl J Med 2008;359:1811–1821

    CAS  PubMed  CrossRef  Google Scholar 

  8. Culleton BF. Uric acid and cardiovascular disease: a renal-cardiac relationship? Curr Opin Nephrol Hypertens 2001;10:371–375

    CAS  PubMed  CrossRef  Google Scholar 

  9. Culleton BF, Larson MG, Kannel WB, Levy D. Serum uric acid and risk for cardiovascular disease and death: the Framingham Heart Study. Ann Internal Med 1999;131:7–13

    CAS  Google Scholar 

  10. Reyes AJ, Leary WP. The ALLHAT and the cardioprotection conferred by diuretics in hypertensive patients: a connection with uric acid? Cardiovasc Drugs Ther 2002;16:485–487

    PubMed  Google Scholar 

  11. Reyes AJ, Leary WP. The increase in serum uric acid induced by diuretics could be beneficial to cardiovascular prognosis in hypertension: a hypothesis. J Hypertension 2003;21:1775–1777

    CAS  CrossRef  Google Scholar 

  12. Nieto FJ, Iribarren C, Gross MD, Comstock GW, Cutler RG. Uric acid and serum antioxidant capacity: a reaction to atherosclerosis? Atherosclerosis 2000;148:131–139

    CAS  PubMed  CrossRef  Google Scholar 

  13. Glantzounis GK, Tsimoyiannis EC, Kappas AM, Galaris DA. Uric acid and oxidative stress. Curr Pharm Des 2005;11:4145–4151

    CAS  PubMed  CrossRef  Google Scholar 

  14. Johnson RJ, Feig DI, Herrera-Acosta J, Kang DH. Resurrection of uric acid as a causal risk factor in essential hypertension. Hypertension 2005;45:18–20

    CAS  PubMed  CrossRef  Google Scholar 

  15. Sautin YY, Johnson RJ. Uric acid: the oxidant-antioxidant paradox. Nucleosides Nucleotides Nucleic Acids 2008;27:608–619

    CAS  PubMed  CrossRef  Google Scholar 

  16. Sautin YY, Nakagawa T, Zharikov S, Johnson RJ. Adverse effects of the classic antioxidant uric acid in adipocytes: NADPH oxidase-mediated oxidative/nitrosative stress. Am J Physiol Cell Physiol 2007;293:C584–C596

    CAS  PubMed  CrossRef  Google Scholar 

  17. Becker BF. Towards the physiological function of uric acid. Free Radic Biol Med 1993;14:615–631

    CAS  PubMed  CrossRef  Google Scholar 

  18. Simie M, Jovanovic S. Antioxidation mechanisms of uric acid. J Am Chem Soc 1989;111:5778–5782

    CrossRef  Google Scholar 

  19. Rosell M, Regnstrom J, Kallner A, Hellenius ML. Serum urate determines antioxidant capacity in middle-aged men – a controlled, randomized diet and exercise intervention study. J Intern Med 1999;246:219–226

    CAS  PubMed  CrossRef  Google Scholar 

  20. Maples KR, Mason RP. Free radical metabolite of uric acid. J Biol Chem 1988;263:1709–1712

    CAS  PubMed  Google Scholar 

  21. Vasquez-Vivar J, Santos AM, Junqueira VB, Augusto O. Peroxynitrite-mediated formation of free radicals in human plasma: EPR detection of ascorbyl, albumin-thiyl and uric acid-derived free radicals. Biochemical J 1996;314(Pt 3):869–876

    CAS  Google Scholar 

  22. Santos CX, Anjos EI, Augusto O. Uric acid oxidation by peroxynitrite: multiple reactions, free radical formation, and amplification of lipid oxidation. Arch Biochem Biophys 1999;372:285–294

    CAS  PubMed  CrossRef  Google Scholar 

  23. Hellsten Y, Tullson PC, Richter EA, Bangsbo J. Oxidation of urate in human skeletal muscle during exercise. Free Radic Biol Med 1997;22:169–174

    CAS  PubMed  CrossRef  Google Scholar 

  24. Mikami T, Kita K, Tomita S, et al. Is allantoin in serum and urine a useful indicator of exercise-induced oxidative stress in humans? Free Radic Res 2000;32:235–244

    CAS  PubMed  CrossRef  Google Scholar 

  25. Doehner W, Schoene N, Rauchhaus M, et al. Effects of xanthine oxidase inhibition with allopurinol on endothelial function and peripheral blood flow in hyperuricemic patients with chronic heart failure: results from 2 placebo-controlled studies. Circulation 2002;105:2619–2624

    CAS  PubMed  CrossRef  Google Scholar 

  26. Grootveld M, Halliwell B. Measurement of allantoin and uric-acid in human-body fluids – a potential index of free-radical reactions in vivo. Biochemical J 1987;243:803–808

    CAS  Google Scholar 

  27. Kand’ar R, Zakova P, Muzakova V. Monitoring of antioxidant properties of uric acid in humans for a consideration measuring of levels of allantoin in plasma by liquid chromatography. Clin Chim Acta 2006;365:249–256

    PubMed  CrossRef  CAS  Google Scholar 

  28. Felici C, Ciari I, Terzuoli L, et al. Purine catabolism in advanced carotid artery plaque. Nucleosides Nucleotides Nucleic Acids 2006;25:1291–1294

    CAS  PubMed  CrossRef  Google Scholar 

  29. Kahn K, Serfozo P, Tipton PA. Identification of the true product of the urate oxidase reaction. J Am Chem Soc 1997;119:5435–5442

    CAS  CrossRef  Google Scholar 

  30. Radi R, Peluffo G, Alvarez MN, Naviliat M, Cayota A. Unraveling peroxynitrite formation in biological systems. Free Radic Biol Med 2001;30:463–488

    CAS  PubMed  CrossRef  Google Scholar 

  31. Robinson KM, Morre JT, Beckman JS. Triuret: a novel product of peroxynitrite-mediated oxidation of urate. Arch Biochem Biophys 2004;423:213–217

    CAS  PubMed  CrossRef  Google Scholar 

  32. Kuzkaya N, Weissmann N, Harrison DG, Dikalov S. Interactions of peroxynitrite with uric acid in the presence of ascorbate and thiols: implications for uncoupling endothelial nitric oxide synthase. Biochem Pharmacol 2005;70:343–354

    CAS  PubMed  CrossRef  Google Scholar 

  33. Gersch C, Palii SP, Imaram W, et al. Reactions of peroxynitrite with uric acid: formation of reactive intermediates, alkylated products and triuret, and in vivo production of triuret under conditions of oxidative stress. Nucleosides Nucleotides Nucleic Acids 2009;28:118–149

    CAS  PubMed  CrossRef  Google Scholar 

  34. Kim KM, Henderson GN, Frye RF, et al. Simultaneous determination of uric acid metabolites allantoin, 6-aminouracil, and triuret in human urine using liquid chromatography-mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2009;877:65–70

    CAS  PubMed  CrossRef  Google Scholar 

  35. Skinner KA, White CR, Patel R, et al. Nitrosation of uric acid by peroxynitrite. Formation of a vasoactive nitric oxide donor. J Biol Chem 1998;273:24491–24497

    CAS  PubMed  CrossRef  Google Scholar 

  36. Gersch C, Palii SP, Imaram W, Kim KM, Karumanchi SA, Angerhofer A, Johnson RJ, Henderson GN. Reactions of peroxynitrite with uric acid: formation of reactive intermediates, alkylated products and triuret, and in vivo production of triuret under conditions of oxidative stress. Nucleosides Nucleotides Nucleic Acids 2009;28:118–149

    Google Scholar 

  37. Suzuki T. Nitrosation of uric acid induced by nitric oxide under aerobic conditions. Nitric Oxide 2007;16:266–273

    CAS  PubMed  CrossRef  Google Scholar 

  38. Gersch C, Palii SP, Kim KM, et al. Inactivation of nitric oxide by uric acid. Nucleosides Nucleotides Nucleic Acids 2008;27:967–978

    CAS  PubMed  CrossRef  Google Scholar 

  39. Waugh WH. Inhibition of iron-catalyzed oxidations by attainable uric acid and ascorbic acid levels: therapeutic implications for Alzheimer’s disease and late cognitive impairment. Gerontology 2008;54:238–243

    CAS  PubMed  CrossRef  Google Scholar 

  40. Schlotte V, Sevanian A, Hochstein P, Weithmann KU. Effect of uric acid and chemical analogues on oxidation of human low density lipoprotein in vitro. Free Radic Biol Med 1998;25:839–847

    CAS  PubMed  CrossRef  Google Scholar 

  41. Muraoka S, Miura T. Inhibition by uric acid of free radicals that damage biological molecules. Pharmacol Toxicol 2003;93:284–289

    CAS  PubMed  CrossRef  Google Scholar 

  42. Hink HU, Santanam N, Dikalov S, et al. Peroxidase properties of extracellular superoxide dismutase: role of uric acid in modulating in vivo activity. Arterioscler Thromb Vasc Biol 2002;22:1402–1408

    CAS  PubMed  CrossRef  Google Scholar 

  43. Sevanian A, Davies KJ, Hochstein P. Conservation of vitamin C by uric acid in blood. J Free Radic Biol Med 1985;1:117–124

    CAS  PubMed  CrossRef  Google Scholar 

  44. Sevanian A, Davies KJ, Hochstein P. Serum urate as an antioxidant for ascorbic acid. Am J Clin Nutr 1991;54:1129S–1134S

    CAS  PubMed  Google Scholar 

  45. Frei B, Stocker R, Ames BN. Antioxidant defenses and lipid peroxidation in human blood plasma. Proc Natl Acad Sci USA 1988;85:9748–9752

    CAS  PubMed  CrossRef  Google Scholar 

  46. Waring WS, Convery A, Mishra V, et al. Uric acid reduces exercise-induced oxidative stress in healthy adults. Clin Sci (Lond) 2003;105:425–430

    CAS  CrossRef  Google Scholar 

  47. Waring WS, McKnight JA, Webb DJ, Maxwell SR. Uric acid restores endothelial function in patients with type 1 diabetes and regular smokers. Diabetes 2006;55:3127–3132

    CAS  PubMed  CrossRef  Google Scholar 

  48. Waring WS, Webb DJ, Maxwell SR. Systemic uric acid administration increases serum antioxidant capacity in healthy volunteers. J Cardiovasc Pharmacol 2001;38:365–371

    CAS  PubMed  CrossRef  Google Scholar 

  49. Kurra V, Eraranta A, Jolma A, et al. Hyperuricemia, oxidative stress, and carotid artery tone in experimental renal insufficiency. Am J Hypertens 2009;22:694–970

    CrossRef  CAS  Google Scholar 

  50. Schlesinger I, Schlesinger N. Uric acid in Parkinson’s disease. Mov Disord 2008;23:1653–1657

    PubMed  CrossRef  Google Scholar 

  51. Chen H, Mosley TH, Alonso A, Huang X. Plasma urate and Parkinson’s disease in the Atherosclerosis Risk in Communities (ARIC) study. Am J Epidemiol 2009;169:1064–1069

    PubMed  CrossRef  Google Scholar 

  52. Hooper DC, Spitsin S, Kean RB, et al. Uric acid, a natural scavenger of peroxynitrite, in experimental allergic encephalomyelitis and multiple sclerosis. Proc Natl Acad Sci USA 1998;95:675–680

    CAS  PubMed  CrossRef  Google Scholar 

  53. Guerreiro S, Ponceau A, Toulorge D, et al. Protection of midbrain dopaminergic neurons by the end-product of purine metabolism uric acid: potentiation by low-level depolarization. J Neurochem 2009;109:1118–1128

    CAS  PubMed  CrossRef  Google Scholar 

  54. Yu ZF, Bruce-Keller AJ, Goodman Y, Mattson MP. Uric acid protects neurons against excitotoxic and metabolic insults in cell culture, and against focal ischemic brain injury in vivo. J Neurosci Res 1998;53:613–625

    CAS  PubMed  CrossRef  Google Scholar 

  55. Church WH, Ward VL. Uric acid is reduced in the substantia nigra in Parkinson’s disease: effect on dopamine oxidation. Brain Res Bull 1994;33:419–425

    CAS  PubMed  CrossRef  Google Scholar 

  56. Hooper DC, Scott GS, Zborek A, et al. Uric acid, a peroxynitrite scavenger, inhibits CNS inflammation, blood-CNS barrier permeability changes, and tissue damage in a mouse model of multiple sclerosis. FASEB J 2000;14:691–698

    CAS  PubMed  Google Scholar 

  57. Spitsin SV, Scott GS, Mikheeva T, et al. Comparison of uric acid and ascorbic acid in protection against EAE. Free Radic Biol Med 2002;33:1363–1371

    CAS  PubMed  CrossRef  Google Scholar 

  58. Kim SY, Guevara JP, Kim KM, et al. Hyperuricemia and risk of stroke: a systematic review and meta-analysis. Arthritis Rheum 2009;61:885–892

    PubMed  CrossRef  Google Scholar 

  59. Tsukada K, Hasegawa T, Tsutsumi S, et al. Effect of uric acid on liver injury during hemorrhagic shock. Surgery 2000;127:439–446

    CAS  PubMed  CrossRef  Google Scholar 

  60. Becker BF, Reinholz N, Ozcelik T, Leipert B, Gerlach E. Uric acid as radical scavenger and antioxidant in the heart. Pflugers Arch 1989;415:127–135

    CAS  PubMed  CrossRef  Google Scholar 

  61. Price KL, Sautin YY, Long DA, et al. Human vascular smooth muscle cells express a urate transporter. J Am Soc Nephrol 2006;17:1791–1795

    CAS  PubMed  CrossRef  Google Scholar 

  62. Kang DH, Han L, Ouyang X, et al. Uric acid causes vascular smooth muscle cell proliferation by entering cells via a functional urate transporter. Am J Nephrol 2005;25:425–433

    CAS  PubMed  CrossRef  Google Scholar 

  63. Abuja PM. Ascorbate prevents prooxidant effects of urate in oxidation of human low density lipoprotein. FEBS Lett 1999;446:305–308

    CAS  PubMed  CrossRef  Google Scholar 

  64. Sanguinetti SM, Batthyany C, Trostchansky A, et al. Nitric oxide inhibits prooxidant actions of uric acid during copper-mediated LDL oxidation. Arch Biochem Biophys 2004;423:302–308

    CAS  PubMed  CrossRef  Google Scholar 

  65. Imaram W. PhD Thesis, University of Florida 2008

    Google Scholar 

  66. Corry DB, Eslami P, Yamamoto K, et al. Uric acid stimulates vascular smooth muscle cell proliferation and oxidative stress via the vascular renin-angiotensin system. J Hypertens 2008;26:269–275

    CAS  PubMed  CrossRef  Google Scholar 

  67. Kanellis J, Watanabe S, Li JH, et al. Uric acid stimulates monocyte chemoattractant protein-1 production in vascular smooth muscle cells via mitogen-activated protein kinase and cyclooxygenase-2. Hypertension 2003;41:1287–1293

    CAS  PubMed  CrossRef  Google Scholar 

  68. Sanchez-Lozada LG, Soto V, Tapia E, et al. Role of oxidative stress in the renal abnormalities induced by experimental hyperuricemia. Am J Physiol 2008;295:F1134–F1141

    CAS  CrossRef  Google Scholar 

  69. Pacher P, Nivorozhkin A, Szabo C. Therapeutic effects of xanthine oxidase inhibitors: renaissance half a century after the discovery of allopurinol. Pharmacol Rev 2006;58:87–114

    CAS  PubMed  CrossRef  Google Scholar 

  70. Harrison R. Physiological roles of xanthine oxidoreductase. Drug Metab Rev 2004;36:363–375

    CAS  PubMed  CrossRef  Google Scholar 

  71. Berry CE, Hare JM. Xanthine oxidoreductase and cardiovascular disease: molecular mechanisms and pathophysiological implications. J Physiol 2004;555:589–606

    CAS  PubMed  CrossRef  Google Scholar 

  72. Galbusera C, Orth P, Fedida D, Spector T. Superoxide radical production by allopurinol and xanthine oxidase. Biochem Pharmacol 2006;71:1747–1752

    CAS  PubMed  CrossRef  Google Scholar 

  73. Spector T. Oxypurinol as an inhibitor of xanthine oxidase-catalyzed production of superoxide radical. Biochem Pharmacol 1988;37:349–352

    CAS  PubMed  CrossRef  Google Scholar 

  74. Cannon PJ, Stason WB, Demartini FE, Sommers SC, Laragh JH. Hyperuricemia in primary and renal hypertension. N Engl J Med 1966;275:457–464

    CAS  PubMed  CrossRef  Google Scholar 

  75. Feig DI, Johnson RJ. Hyperuricemia in childhood primary hypertension. Hypertension 2003;42:247–252

    CAS  PubMed  CrossRef  Google Scholar 

  76. Mazzali M, Hughes J, Kim YG, et al. Elevated uric acid increases blood pressure in the rat by a novel crystal-independent mechanism. Hypertension 2001;38:1101–1106

    CAS  PubMed  CrossRef  Google Scholar 

  77. Mazzali M, Kanellis J, Han L, et al. Hyperuricemia induces a primary renal arteriolopathy in rats by a blood pressure-independent mechanism. Am J Physiol 2002;282:F991–F997

    CAS  Google Scholar 

  78. Sanchez-Lozada LG, Tapia E, Lopez-Molina R, et al. Effects of acute and chronic L-arginine treatment in experimental hyperuricemia. Am J Physiol 2007;292:F1238–F1244

    CAS  Google Scholar 

  79. Feig DI, Soletsky B, Johnson RJ. Effect of allopurinol on the blood pressure of adolescents with newly diagnosed essential hypertension. JAMA 2008;300:922–930

    CrossRef  Google Scholar 

  80. George J, Carr E, Davies J, Belch JJ, Struthers A. High-dose allopurinol improves endothelial function by profoundly reducing vascular oxidative stress and not by lowering uric acid. Circulation 2006;114:2508–2516

    CAS  PubMed  CrossRef  Google Scholar 

  81. Facchini F, Chen YD, Hollenbeck CB, Reaven GM. Relationship between resistance to insulin-mediated glucose uptake, urinary uric acid clearance, and plasma uric acid concentration. JAMA 1991;266:3008–3011

    CAS  PubMed  CrossRef  Google Scholar 

  82. Quinones GA, Natali A, Baldi S, et al. Effect of insulin on uric acid excretion in humans. Am J Physiol 1995;268:E1–E5

    Google Scholar 

  83. Johnson RJ, Perez-Pozo SE, Sautin YY, et al. Hypothesis: could excessive fructose intake and uric acid cause type 2 diabetes? Endocr Rev 2009;30:96–116

    CAS  PubMed  CrossRef  Google Scholar 

  84. Stirpe F, Della Corte E, Bonetti E, et al. Fructose-induced hyperuricaemia. Lancet 1970;2:1310–1311

    CAS  CrossRef  Google Scholar 

  85. Nakagawa T, Hu H, Zharikov S, et al. A causal role for uric acid in fructose-induced metabolic syndrome. Am J Physiol 2006;290:F625–F631

    CAS  Google Scholar 

  86. Reungjui S, Roncal CA, Mu W, et al. Thiazide diuretics exacerbate fructose-induced metabolic syndrome. J Am Soc Nephrol 2007;18:2724–2731

    CAS  PubMed  CrossRef  Google Scholar 

  87. Furukawa S, Fujita T, Shimabukuro M, et al. Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest 2004;114:1752–1761

    CAS  PubMed  Google Scholar 

  88. Cheung KJ, Tzameli I, Pissios P, et al. Xanthine oxidoreductase is a regulator of adipogenesis and PPARgamma activity. Cell Metab 2007;5:115–128

    CAS  PubMed  CrossRef  Google Scholar 

  89. Perez-Pozo SE, Schold J, Nakagawa T, SÃnchez-Lozada LG, Johnson RJ, Lillo JL. Excessive fructose intake induces the features of metabolic syndrome in healthy adult men: role of uric acid in the hypertensive response. Int J Obes (Lond) 2010;34:454–461.

    Google Scholar 

  90. Hsu SP, Pai MF, Peng YS, et al. Serum uric acid levels show a “J-shaped” association with all-cause mortality in haemodialysis patients. Nephrol Dial Transplant 2004;19:457–462

    CAS  PubMed  CrossRef  Google Scholar 

  91. Suliman ME, Johnson RJ, Garcia-Lopez E, et al. J-shaped mortality relationship for uric acid in CKD. Am J Kidney Dis 2006;48:761–771

    CAS  PubMed  CrossRef  Google Scholar 

  92. Lee SM, Lee AL, Winters TJ, et al. Low serum uric acid level is a risk factor for death in incident hemodialysis patients. Am J Nephrol 2009;29:79–85

    CAS  PubMed  CrossRef  Google Scholar 

  93. Nakagawa T, Mazzali M, Kang DH, et al. Hyperuricemia causes glomerular hypertrophy in the rat. Am J Nephrol 2003;23:2–7

    PubMed  CrossRef  Google Scholar 

  94. Kang DH, Nakagawa T, Feng L, et al. A role for uric acid in the progression of renal disease. J Am Soc Nephrol 2002;13:2888–2897

    CAS  PubMed  CrossRef  Google Scholar 

  95. Sanchez-Lozada LG, Tapia E, Avila-Casado C, et al. Mild hyperuricemia induces glomerular hypertension in normal rats. Am J Physiol 2002;283:F1105–F1110

    Google Scholar 

  96. Sanchez-Lozada LG, Tapia E, Bautista-Garcia P, et al. Effects of febuxostat on metabolic and renal alterations in rats with fructose-induced metabolic syndrome. Am J Physiol 2008;294:F710–F718

    CAS  CrossRef  Google Scholar 

  97. Sanchez-Lozada LG, Tapia E, Santamaria J, et al. Mild hyperuricemia induces vasoconstriction and maintains glomerular hypertension in normal and remnant kidney rats. Kidney Int 2005;67:237–247

    PubMed  CrossRef  Google Scholar 

  98. Sanchez-Lozada LG, Tapia E, Soto V, et al. Effect of febuxostat on the progression of renal disease in 5/6 nephrectomy rats with and without hyperuricemia. Nephron Physiol 2008;108:69–78

    CrossRef  CAS  Google Scholar 

  99. Roncal CA, Mu W, Croker B, et al. Effect of elevated serum uric acid on cisplatin-induced acute renal failure. Am J Physiol 2007;292:F116–F122

    CAS  Google Scholar 

  100. Kosugi T, Nakayama T, Heinig M, Zhang L, Yuzawa Y, Sanchez-Lozada LG, Roncal C, Johnson RJ, Nakagawa T. Effect of lowering uric acid on renal disease in the type 2 diabetic db/db mice. Am J Physiol Renal Physiol 2009;297:F481–F488

    Google Scholar 

  101. Iseki K, Ikemiya Y, Inoue T, et al. Significance of hyperuricemia as a risk factor for developing ESRD in a screened cohort. Am J Kidney Dis 2004;44:642–650

    PubMed  Google Scholar 

  102. Iseki K, Oshiro S, Tozawa M, et al. Significance of hyperuricemia on the early detection of renal failure in a cohort of screened subjects. Hypertens Res 2001;24:691–697

    CAS  PubMed  CrossRef  Google Scholar 

  103. Rosolowsky ET, Ficociello LH, Maselli NJ, et al. High-normal serum uric acid is associated with impaired glomerular filtration rate in nonproteinuric patients with type 1 diabetes. Clin. J Am Soc Nephrol 2008;3:706–713

    CAS  PubMed  CrossRef  Google Scholar 

  104. Hovind P, Rossing P, Tarnow L, Johnson RJ, Parving HH. Serum uric acid as a predictor for development of diabetic nephropathy in type 1 diabetes: an inception cohort study. Diabetes 2009;58:1668–1671

    CAS  PubMed  CrossRef  Google Scholar 

  105. Syrjanen J, Mustonen J, Pasternack A. Hypertriglyceridaemia and hyperuricaemia are risk factors for progression of IgA nephropathy. Nephrol Dial Transplant 2000;15:34–42

    CAS  PubMed  CrossRef  Google Scholar 

  106. Ohno I, Hosoya T, Gomi H, et al. Serum uric acid and renal prognosis in patients with IgA nephropathy. Nephron 2001;87:333–339

    CAS  PubMed  CrossRef  Google Scholar 

  107. Madero M, Sarnak MJ, Wang X, et al. Uric acid and long-term outcomes in CKD. Am J Kidney Dis 2009;53:796–803

    CAS  PubMed  CrossRef  Google Scholar 

  108. Siu YP, Leung KT, Tong MK, Kwan TH. Use of allopurinol in slowing the progression of renal disease through its ability to lower serum uric acid level. Am J Kidney Dis 2006;47:51–59

    CAS  PubMed  CrossRef  Google Scholar 

  109. Talaat KM, El-Sheikh AR. The effect of mild hyperuricemia on urinary transforming growth factor beta and the progression of chronic kidney disease. Am J Nephrol 2007;27:435–440

    CAS  PubMed  CrossRef  Google Scholar 

  110. Chao HH, Liu JC, Lin JW, et al. Uric acid stimulates endothelin-1 gene expression associated with NADPH oxidase in human aortic smooth muscle cells. Acta Pharmacol Sin 2008;29:1301–1312

    CAS  PubMed  CrossRef  Google Scholar 

  111. Cheng TH, Lin JW, Chao HH, Chen YL, Chen CH, Chan P, Liu JC. Uric acid activates extracellular signal-regulated kinases and thereafter endothelin-1 expression in rat cardiac fibroblasts. Int J Cardiol 2010:139:42–49

    Google Scholar 

  112. Roncal CA, Reungjui S, SÃnchez-Lozada LG, Mu W, Sautin YY, Nakagawa T, Johnson RJ. Combination of captopril and allopurinol retards fructose-induced metabolic syndrome. Am J Nephrol 2009;30:399–404

    Google Scholar 

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Sautin, Y.Y., Imaram, W., Kim, K.M., Angerhofer, A., Henderson, G., Johnson, R. (2011). Uric Acid and Oxidative Stress. In: Miyata, T., Eckardt, KU., Nangaku, M. (eds) Studies on Renal Disorders. Oxidative Stress in Applied Basic Research and Clinical Practice. Humana Press. https://doi.org/10.1007/978-1-60761-857-7_8

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