Multiple skleroz hastalarında serum paraoksonaz ve arilesteraz aktiviteleri ile oksidatif stresin araştırılması

Amaç: Oksidatif stresin multiple skleroz (MS)’un patojenezinin önemli bir komponenti olduğu ile ilgili gittikçe artan sayıda kanıt vardır. Paraoksonaz 1 (PON1) plazma yüksek-dansiteli lipoproteine (HDL) bağlı bir antioksidan enzimdir. Onun düşük-dansiteli lipoprotein (LDL) ve HDL’yi oksidasyona karşı koruduğu ve oksidatif stresi azalttığı gösterilmiştir. Bu çalışmanın amacı oksidatif stres ve MS hastalığı arasındaki ilişkiyi araştırmaktır. Yöntem: Elli MS hastası (17E, 33K) ve 35 sağlıklı kontrolün (15E, 20K) serum PON1 ve arilesteraz aktiviteleri ile total antioksidan durum (TAS) ve total oksidan durum (TOS) seviyeleri karşılaştırıldı. Bulgular: MS hastalarının TAS seviyeleri sağlıklı kontrollerden anlamlı derecede düşüktü (p

Investigation of serum paraoxonase and arylesterase activities and oxidative stress in patients with multiple sclerosis

Objective: There is increasing evidence that oxidative stress is an important component in the pathogenesis of multiple sclerosis (MS). Paraoxonase 1 (PON1) is an antioxidant enzyme bound to plasma high-density lipoprotein (HDL). It has been shown to protect low-density lipoprotein (LDL) and HDL against oxidation and can reduce oxidative stress. The aim of this study was to investigate the relationship between oxidative stress and MS. Methods: We compared serum PON1 and arylesterase activities and total antioxidant status (TAS) and total oxidant status (TOS) levels of 50 patients with MS (17M, 33F) and 35 age-matched healthy controls (15M, 20F). Results: TAS levels of MS patients were significantly lower than that of controls (P<0.05). TOS levels of MS patients were higher and PON1 and arylesterase activities of MS patients were lower, but not significantly, than those of controls. Conclusion: Although underlying mechanism of TAS levels of MS patients were significantly reduced compared to those of controls, it implies that endogenous antioxidants may have been exhausted by increased oxidative stress and we believe that additional antioxidant treatment might be beneficial for these patients.

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  • 1. Hafler DA, Slavik JM, Anderson DE, O'Connor KC, De Jager P, Baecher-Allan C. Multiple sclerosis. Immunol Rev 2005;204:208-31.
  • 2. İdiman E. Multipl Skleroz'un immunopatogenezi. Turkiye Klinikleri J Neur 2004;2;171-176.
  • 3. Gonsette RE. Neurodegeneration in multiple sclerosis: The role of oxidative stress and excitotoxicity. J Neurol Sci 2008;274:48-53.
  • 4. Gilgun-Sherki Y, Melamed E, Offen D. The role of oxidative stress in the pathogenesis of multiple sclerosis: the need for effective antioxidant therapy. J Neurol 2004;251:261-8.
  • 5. Ortiz GG, Macías-Islas MA, Pacheco-Moisés FP, Cruz-Ramos JA, Sustersik S, Barba EA, et al. Oxidative stress is increased in serum from Mexican patients with relapsing-remitting multiple sclerosis. Dis Markers 2009;26:35-9.
  • 6. Koch M, Mostert J, Arutjunyan AV, Stepanov M, Teelken A, Heersema D, et al. Plasma lipid peroxidation and progression of disability in multiple sclerosis. Eur J Neurol 2007;14:529- 33.
  • 7. Besler HT, Comoğlu S, Okçu Z. Serum levels of antioxidant vitamins and lipid peroxidation in multiple sclerosis. Nutr Neurosci 2002;5:215-20.
  • 8. Besler HT, Comoğlu S. Lipoprotein oxidation, plasma total antioxidant capacity and homocysteine level in patients with multiple sclerosis. Nutr Neurosci 2003;6:189-96.
  • 9. Koch M, Ramsaransing GS, Arutjunyan AV, Stepanov M, Teelken A, Heersema DJ, et al. Oxidative stress in serum and peripheral blood leukocytes in patients with different disease courses of multiple sclerosis. J Neurol 2006;253:483-7.
  • 10. Syburra C, Passi S. Oxidative stress in patients with multiple sclerosis. Ukr Biokhim Zh 1999;71:112-5.
  • 11. Koch M, Mostert J, Arutjunyan AV, Stepanov M, Teelken A, Heersema D, et al. Plasma lipid peroxidation and progression of disability in multiple sclerosis. Eur J Neurol 2007;14:529- 33.
  • 12. Mackness MI, Mackness B, Durrington PN, Connelly PW, Hegele RA. Paraoxonase: biochemistry, genetics and relationship to plasma lipoproteins. Curr Opin Lipidol 1996;7:69-76.
  • 13. Balcı Ekmekçi Ö, Donma O, Ekmekçi H. Paraokonaz. Cerrahpaşa Tıp Derg 2004;35:78-82.
  • 14. Draganov DI, La Du BN. Pharmacogenetics of paraoxonases: a brief review. Naunyn Schmiedebergs Arch Pharmacol 2004;369:78-88.
  • 15. Deakin SP, James RW. Genetic and environmental factors modulating serum concentrations and activities of the antioxidant enzyme paraoxonase-1. Clin Sci (Lond) 2004;107:435-47.
  • 16. Erel O. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clin Biochem 2004;37: 277-85.
  • 17. Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem 2005;38:1103-11.
  • 18. Jamroz-Wisniewska A, Beltowski J, Stelmasiak Z, Bartosik- Psujek H. Paraoxonase 1 activity in different types of multiple sclerosis. Mult Scler 2009;15:399-402.
  • 19. Ferretti G, Bacchetti T, Principi F, Di Ludovico F, Viti B, Angeleri VA, et al. Increased levels of lipid hydroperoxides in plasma of patients with multiple sclerosis: a relationship with paraoxonase activity. Mult Scler 2005;11:677-82.
  • 20. McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol. 2001;50:121- 7.
  • 21. Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983;33:1444-52.
  • 22. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972;18:499-502.
  • 23. Eckerson HW, Wyte CM, La Du BN. The human serum paraoxonase/arylesterase polymorphism. Am J Hum Genet 1983;35:1126-38.
  • 24. Haagen L, Brock A. A new automated method for phenotyping arylesterase (E.C.3.1.1.2.) based upon inhibition of enzymatic hydrolysis of 4-nitrophenyl acetate by phenyl acetate. Eur J Clin Chem Clin Biochem 1992;30:391-5.
  • 25. Seres I, Paragh G, Deschene E, Fulop T Jr, Khalil A. Study of factors influencing the decreased HDL associated PON1 activity with aging. Exp Gerontol 2004;39:59-66.
  • 26. HypJiménez-Jiménez FJ, de Bustos F, Molina JA, de Andrés C, Gasalla T, Ortí-Pareja M, et al. Cerebrospinal fluid levels of alpha-tocopherol in patients with multiple sclerosis. Neurosci Lett 1998;249:65-7.
  • 27. Nguyen SD, Sok DE. Oxidative inactivation of paraoxonase1, an antioxidant protein and its effect on antioxidant action. Free Radic Res 2003;37:1319-30.
  • 28. Aviram M, Rosenblat M. Paraoxonases 1, 2, and 3, oxidative stress, and macrophage foam cell formation during atherosclerosis development. Free Radic Biol Med 2004;37:1304-16.