Evaluation of the role of serum uric acid in patients with multiple sclerosis; An Observational case-control study
DOI:
https://doi.org/10.22317/imj.v3i4.721Keywords:
Multiple sclerosis, Uric acid, Nitric oxide, PeroxynitriteAbstract
Objectives: To evaluate the role of uric acid in patients with MS as an investigational marker in true relapse events.
Methods: 108 patients with relapsing-remitting and Secondary progressive MS, compared to case-control of about 120 patients (manifested other neurological diseases OND) who were included in this study which was conducted from March 2008 to July 2009 at Baghdad Teaching Hospital multiple sclerosis clinic. A study protocol sheet was done and filled from the patient's database in the MS clinic.
Results: In the overall MS group, serum UA levels were lower than in controls, the difference did reach statistical significance (P=0.01). Serum UA was found to be lower in patients during relapse than when they are in remission. The mean serum UA level from patients after one month of follow up shows an inverse correlation with MS type, age, and EDSS score, and positive correlation with gender and clinical activity, but none of these correlations reach statistical significance.
Conclusions: The question whether reduced serum UA level in MS is a primary deficit or an epiphenomenon remains open. Despite the fact that UA level was lower in clinically-documented active patients, a general mean UA decrease is evident also in clinically and MRI inactive MS patients as compared to OND.
References
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24. Koprowski H, Spitsin SV, Hooper DC. Prospects for the treatment of multiple sclerosis by raising serum levels of uric acid, a scavenger of peroxynitrite. Ann Neurol. 2001 Jan; 49(1):139.
25. Drulović J, Dujmović I, Stojsavljević N, et al. Uric acid levels in sera from patients with multiple sclerosis. J Neurol. 2001 Feb; 248(2):121-6.
26. Karg E, Klivényi P, Németh I, Bencsik K, Pintér S, Vécsei L. Nonenzymatic antioxidants of blood in multiple sclerosis. J Neurol. 1999 Jul; 246(7):533-9.
27. Constantinescu CS, Freitag P, Kappos L. Increase in serum levels of uric acid, an endogenous antioxidant, under treatment with glatiramer acetate for multiple sclerosis. Mult Scler. 2000 Dec; 6(6):378-81.
28. Brück W, Bitsch A, Kolenda H, Brück Y, Stiefel M, Lassmann H. Inflammatory central nervous system demyelination: correlation of magnetic resonance imaging findings with lesion pathology. Ann Neurol. 1997 Nov; 42(5):783-93.
29. 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 Apr; 14(5):691-8.
30. Coles AJ, Wing MG, Molyneux P, et al. Monoclonal antibody treatment exposes three mechanisms underlying the clinical course of multiple sclerosis. Ann Neurol. 1999 Sep; 46(3):296-304.
31. Trapp BD, Peterson J, Ransohoff RM, Rudick R, Mörk S, Bö L. Axonal transection in the lesions of multiple sclerosis. N Engl J Med. 1998 Jan 29; 338(5):278-85.
32. Arnold DL, Riess GT, Matthews PM, et al. Use of proton magnetic resonance spectroscopy for monitoring disease progression in multiple sclerosis. Ann Neurol. 1994 Jul; 36(1):76-82.
33. Arnold DL, Matthews PM, Francis G, Antel J. Proton magnetic resonance spectroscopy of human brain in vivo in the evaluation of multiple sclerosis: assessment of the load of disease. Magn Reson Med. 1990 Apr; 14(1):154-9.
34. Ferguson B, Matyszak MK, Esiri MM, Perry VH. Axonal damage in acute multiple sclerosis lesions. Brain. 1997 Mar; 120 ( Pt 3):393-9.
35. Ring HA, Heller AJ, Marshall WJ, Johnson AL, Reynolds EH. Plasma uric acid in patients receiving anticonvulsant monotherapy. Epilepsy Res. 1991 Apr; 8(3):241-4.
36. Kock R, Delvoux B, Sigmund M, Greiling H. A comparative study of the concentrations of hypoxanthine, xanthine, uric acid and allantoin in the peripheral blood of normals and patients with acute myocardial infarction and other ischemic diseases. Eur J Clin Chem Clin Biochem. 1994 Nov; 32(11):837-42.
37. Ogihara T, Kim HS, Hirano K, et al. Oxidation products of uric acid and ascorbic acid in preterm infants with chronic lung disease. Biol Neonate. 1998; 73(1):24-33.
38. Hellsten Y, Tullson PC, Richter EA, Bangsbo J. Oxidation of urate in human skeletal muscle during exercise. Free Radic Biol Med. 1997; 22(1-2):169-74.
2. "Uric Acid." Biological Magnetic Resonance Data Bank. Indicator Information (gen_metab_summary_5.php-molName=uric_acid.htm#INCHI) Retrieved on 18 February 2008.
3. Lin RF, Lin TS, Tilton RG, Cross AH. Nitric oxide localized to spinal cords of mice with experimental allergic encephalomyelitis: an electron paramagnetic resonance study. J Exp Med. 1993 Aug 1; 178(2):643-8.
4. Hooper DC, Ohnishi ST, Kean R, Numagami Y, Dietzschold B, Koprowski H. Local nitric oxide production in viral and autoimmune diseases of the central nervous system.Proc Natl Acad Sci U S A. 1995Jun 6;92(12):5312-6.
5. Akaike T, Noguchi Y, Ijiri S, et al. Pathogenesis of influenza virus-induced pneumonia: involvement of both nitric oxide and oxygen radicals. Proc Natl Acad Sci U S A. 1996 Mar 19; 93(6):2448-53.
6. Radi R, Beckman JS, Bush KM, Freeman BA. Peroxynitrite-induced membrane lipid peroxidation: the cytotoxic potential of superoxide and nitric oxide. Arch Biochem Biophys. 1991 Aug 1; 288(2):481-7.
7. Beckmann JS, Ye YZ, Anderson PG, et al. Extensive nitration of protein tyrosines in human atherosclerosis detected by immunohistochemistry. Biol Chem Hoppe Seyler. 1994 Feb;375(2):81-8.
8. Ischiropoulos H, Zhu L, Chen J, et al. Peroxynitrite-mediated tyrosine nitration catalyzed by superoxide dismutase. Arch Biochem Biophys. 1992 Nov 1; 298(2):431-7.
9. Whiteman M, Halliwell B. Protection against peroxynitrite-dependent tyrosine nitration and alpha 1-antiproteinase inactivation by ascorbic acid. A comparison with other biological antioxidants. Free Radic Res. 1996 Sep; 25(3):275-83.
10. Hooper DC, Bagasra O, Marini JC, et al. Prevention of experimental allergic encephalomyelitis by targeting nitric oxide and peroxynitrite: implications for the treatment of multiple sclerosis. Proc Natl Acad Sci U S A. 1997 Mar 18; 94(6):2528-33.
11. Huang S, Hendriks W, Althage A, et al. Immune response in mice that lack the interferon-gamma receptor. Science. 1993 Mar 19;259(5102):1742-5.
12. Beckman JS. The double-edged role of nitric oxide in brain function and superoxide-mediated injury. J Dev Physiol. 1991 Jan;15(1):53-9.
13. Cross AH, Misko TP, Lin RF, Hickey WF, Trotter JL, Tilton RG. Aminoguanidine, an inhibitor of inducible nitric oxide synthase, ameliorates experimental autoimmune encephalomyelitis in SJL mice. J Clin Invest. 1994 Jun;93(6):2684-90.
14. Mikkelsen WM, Dodge HJ, Valkengurg H. The distribution of serum uric acid values in a population unselected as to gout or hyperuricemia: Tecumseh, Michigan 1959-1960. Am J Med. 1965 Aug;39:242-51.
15. Smith KJ, Kapoor R, Felts PA. Demyelination: the role of reactive oxygen and nitrogen species. Brain Pathol. 1999 Jan;9(1):69-92.
16. Merrill JE, Ignarro LJ, Sherman MP, Melinek J, Lane TE. Microglial cell cytotoxicity of oligodendrocytes is mediated through nitric oxide. J Immunol. 1993 Aug 15; 151(4):2132-41.
17. Van der Veen RC, Roberts LJ. Contrasting roles for nitric oxide and peroxynitrite in the peroxidation of myelin lipids. J Neuroimmunol. 1999 Mar 1; 95(1-2):1-7.
18. Redford EJ, Kapoor R, Smith KJ. Nitric oxide donors reversibly block axonal conduction: demyelinated axons are especially susceptible. Brain. 1997 Dec; 120 ( Pt 12):2149-57.
19. 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 U S A. 1998 Jan 20; 95(2):675-80.
20. Kastenbauer S, Koedel U, Pfister HW. Role of peroxynitrite as a mediator of pathophysiological alterations in experimental pneumococcal meningitis. J Infect Dis. 1999 Oct; 180(4):1164-70.
21. 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 Sep 1; 53(5):613-25.
22. Van der Veen RC, Hinton DR, Incardonna F, Hofman FM. Extensive peroxynitrite activity during progressive stages of central nervous system inflammation. J Neuroimmunol. 1997 Jul; 77(1):1-7.
23. Kean RB, Spitsin SV, Mikheeva T, Scott GS, Hooper DC. Peroxynitrite scavenger uric acid prevents inflammatory cell invasion into the central nervous system in experimental allergic encephalomyelitis through maintenance of blood-central nervous system barrier integrity. J Immunol. 2000 Dec 1; 165(11):6511 8.
24. Koprowski H, Spitsin SV, Hooper DC. Prospects for the treatment of multiple sclerosis by raising serum levels of uric acid, a scavenger of peroxynitrite. Ann Neurol. 2001 Jan; 49(1):139.
25. Drulović J, Dujmović I, Stojsavljević N, et al. Uric acid levels in sera from patients with multiple sclerosis. J Neurol. 2001 Feb; 248(2):121-6.
26. Karg E, Klivényi P, Németh I, Bencsik K, Pintér S, Vécsei L. Nonenzymatic antioxidants of blood in multiple sclerosis. J Neurol. 1999 Jul; 246(7):533-9.
27. Constantinescu CS, Freitag P, Kappos L. Increase in serum levels of uric acid, an endogenous antioxidant, under treatment with glatiramer acetate for multiple sclerosis. Mult Scler. 2000 Dec; 6(6):378-81.
28. Brück W, Bitsch A, Kolenda H, Brück Y, Stiefel M, Lassmann H. Inflammatory central nervous system demyelination: correlation of magnetic resonance imaging findings with lesion pathology. Ann Neurol. 1997 Nov; 42(5):783-93.
29. 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 Apr; 14(5):691-8.
30. Coles AJ, Wing MG, Molyneux P, et al. Monoclonal antibody treatment exposes three mechanisms underlying the clinical course of multiple sclerosis. Ann Neurol. 1999 Sep; 46(3):296-304.
31. Trapp BD, Peterson J, Ransohoff RM, Rudick R, Mörk S, Bö L. Axonal transection in the lesions of multiple sclerosis. N Engl J Med. 1998 Jan 29; 338(5):278-85.
32. Arnold DL, Riess GT, Matthews PM, et al. Use of proton magnetic resonance spectroscopy for monitoring disease progression in multiple sclerosis. Ann Neurol. 1994 Jul; 36(1):76-82.
33. Arnold DL, Matthews PM, Francis G, Antel J. Proton magnetic resonance spectroscopy of human brain in vivo in the evaluation of multiple sclerosis: assessment of the load of disease. Magn Reson Med. 1990 Apr; 14(1):154-9.
34. Ferguson B, Matyszak MK, Esiri MM, Perry VH. Axonal damage in acute multiple sclerosis lesions. Brain. 1997 Mar; 120 ( Pt 3):393-9.
35. Ring HA, Heller AJ, Marshall WJ, Johnson AL, Reynolds EH. Plasma uric acid in patients receiving anticonvulsant monotherapy. Epilepsy Res. 1991 Apr; 8(3):241-4.
36. Kock R, Delvoux B, Sigmund M, Greiling H. A comparative study of the concentrations of hypoxanthine, xanthine, uric acid and allantoin in the peripheral blood of normals and patients with acute myocardial infarction and other ischemic diseases. Eur J Clin Chem Clin Biochem. 1994 Nov; 32(11):837-42.
37. Ogihara T, Kim HS, Hirano K, et al. Oxidation products of uric acid and ascorbic acid in preterm infants with chronic lung disease. Biol Neonate. 1998; 73(1):24-33.
38. Hellsten Y, Tullson PC, Richter EA, Bangsbo J. Oxidation of urate in human skeletal muscle during exercise. Free Radic Biol Med. 1997; 22(1-2):169-74.
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Published
2019-12-26
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Sheaheed NM, Halomi AM, Almahdawi AM. Evaluation of the role of serum uric acid in patients with multiple sclerosis; An Observational case-control study. Iraq Med J [Internet]. 2019 Dec. 26 [cited 2024 Dec. 25];3(4). Available from: https://iraqmedj.org/index.php/imj/article/view/721
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