SİSTEMİK SKLEROZDA ANTİOKSİDAN TEDAVİLER

Öz

Serbest oksijen radikalleri aşırı miktarda üretildiklerinde oksidatif stres ortaya çıkar. Hücreler ok-sidatif strese karşı intrasellüler antioksidanlar (glutatyon, a-tokoferol, askorbik asit, p-karoten) ve antioksidan enzimler (superoksit dismutaz, katalaz, glutatyon peroksidaz) yoluyla korunurlar. Eğer bu sistem oksidatif stresle mücadele edemezse, hücre hasarı hatta hücre ölümü ortaya çıkar. Serbest radikaller, mikrovasküler endotel hasarı yoluyla sistemik skleroz patogenezinde önemlidirler. Bu kısır döngüyü kırmak için antioksidan maddelerin sistemik sklerozda kullanımını araştıran çeşitli çalışmalar vardır. Bu derlemede sistemik sklerozda antioksidan tedaviler değerlendirildi.

Anahtar Kelimeler

• sistemik skleroz
• oksidatif stres
• antioksidanlar

ANTIOXIDANT TREATMENTS IN SYSTEMIC SCLEROSIS

Öz

Oxidative stres occurs when oxygen free radicals were produced in excess amounts. Cells are protected against oxidative stres with intracellular antioxidants (glutathione, a-tokopherol, ascorbic acid, p-karoten) and antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase). If this system can not come through oxidative stres, cell damage or even cell death occurs. Oyxgen free radicals are important in the pathogenesis of systemic sclerosis by way of microvascular endothelial damage. In order to prevent this viciouc cycle, there are several studies evaluating usage of antioxidants in systemic sclerosis. In this review, antioxidan terapies in systemic sclerosis were evaluated.

Anahtar Kelimeler

• systemic sclerosis
• oxidative stres
• antioxidants

Kaynakça

1. 1. Levy Y, George J, Langevitz P, et al. Elevated homocysteine levels in patients with Raynaud’s syndrome. J Rheumatol 1999;26:2383-5.
2. 2. Rosen A, Casciola-Rosen L, Wigley F. Role of metal-catalysed oxidation reactions in the early pathogenesis of scleroderma. Curr Opinion Rheumatol 1997;9:538-43.
3. 3. Wayner DDM, Burton GW, Ingold KU, Barclay LRC, Locke SJ. The relative contributions of vitamin E, urate, ascorbate and proteins to the peroxylradical trapping । capacity of human blood plasma. Biochem Biophys Acta 1987;924:408-19.r
4. 4 Niwa Y, Somiya K, Michelson AM, Puget K. Effect of liposomal-encapsulated superoxide dismutase on active oxygen-related human disorders. A preliminary study. Free Rad Res Comms 1985;1:137-53.
5. 5. Curcio F, Pecoraro I, Dello Russo P, Faletti E, Perella G, Ceriello A. SOD and GSH inhibit the high glucose induced oxidative damage and the PDGF increased secretion in cultured human endothelial cells. Thromb Haemost 1995;74:969-73.
6. 6. Anderson TJ, Meredith IT, Yeung AC, Frei B, Selwyn AP, Ganz P. The effect of cholesterol lowering and antioxidant therapy on endothelium dependent coronary vasomotion. N Engl J Med 1995;332:488-93.
7. 7. Heitzer T, Just H, Munzel T. Antioxidant vitamin C improves endothelial dysfunction in chronic smokers. Circulation 1996;94:6-9.
8. 8. Hsieh TC, Juan G, Darzynkiewicz Z, Wu JM. Resveratrol increases nitric oxide synthase, induces accumulation of and p53 and p21 (WAF1/C1P1), suppress cultured bovine pulmonary artery endothelial cell proliferation by perturbing progression through S and G2. Cancer Res 1999;59:2511-96.

9. 9. Sato PH, Hall ED. Trilazad mesylate protects vitamin E and C in brain ischemia reperfusion injury. J Neurochem 1992;58:2263-8.
10. 10. Hall Ed, McCall JM, Means ED. Therapeutic potential of the lazaroids (21-aminosteroids) in acute central nervous system trauma, ischemia and subarachnoid hemorrhage. Adv Pharmacol 1994;28:221-65.
11. 11. Simonini G, Alberto P, Sergio G, Fernanda F, Matucci Cerinic M. Emerging potentials for an antioxidant therapy as a new approach to the treatment of systemic sclerosis. Toxicology 2000;155:1-
12. 12. Negre-Salvayre A, Mabile L, Delchambre J, Salvayre R. Alpha-Tocopherol, ascorbic acid, and rutin inhibit synergistically the copper-promoted LDL oxidation and the cytotoxicity of oxidised LDL to cultured endothelial cells. Biol Trace Elem Res 1995;47:81-91.
13. 13. Ferrero ME, Bertelli AE, Fulgenzi A, et al. Activity in vitro of resveratrol on granulocyte adhesion to endothelium. Am.J. Clin. Nutr. 1998;68:1208-14.
14. 14. Ide N, Lau BH. S-allylcysteine attenuates oxidative stress in endothelial cells. Drug Dev Ind Pharm 1999;25:619-24.
15. 15. Weber C, Erl W, Weber K, Weber PC. Increased adhesiveness of isolated monocytes to endothelium is prevented by vitamin C intake in smokers. Circulation 1996; 148892.
16. 16. Lehr HA, Frei B, Olofsson AM, Carew TE, Arfors KE. Protection from oxidised LDL-in-duced leukocyte adhesion to microvascular and macrovascular endothelium in vivo by vitamin C but not by vitamin E. Circulation 1995;91:1525-32.
17. 17. Chaudiere J, Moutet M, D’Alessio R Antioxidant and antiinflammatory protection of vascular endothelial cells by new synthetic mimics of glutathione peroxidase. C R Sae-nces Soc Biol Fill 1995;189:861-82.
18. 18. Denton CP, Bunce TD, Wilson H, Howell K, Bruckdorfer KR, Black CM. Antioxidant therapy for Raynaud’s phenomenonia controlled trial comparing probucol with nifedipine. Arth Rheum 1995;38(suppl.), S152.
19. 19. Sturgill MG, Seibold JR. Rational use of calcium channel antagonists in Raynaud’s phenomenon. Curr Opinion Rheumatol 1998;10:584-8.
20. 20. Mak IT, Weglicki WB. Antioxidant activity of calcium channel blocking drugs. Methods Enzymol 1994;234:620-30.
21. 21. Hainle H, Wulfroth P, Quack G, Lang F. Effects of the new antioxidant nicanartine in an experimental model of atherosclerosis. Arz-neim 1996;46:956-9.
22. 22. Wang XD, Deng XM, Hareldsen P, Andersson R, Ihse I. Antioxidant and calcium channel blockers counteract endothelial barrier injury induced by acute pancreatitis in rats. Scand J Gast 1995;30:1129-36.
23. 23. Rosato E, Borghese F, Pisarri S, Salsano F. The treatment with N-acetylcysteine of Raynaud’s phenomenon and ischemic ulcers therapy in sclerodermic patients: a prospective observational study of 50 patients. Clin Rheumatol. 2009;28(12):1379-84.
24. 24. Fiori G, Galluccio F, Braschi F, Amanzi L, Miniati I, Conforti ML, Del Rosso A, Ge-nerini S, Candelieri A, Magonio A, Goretti R, Rasero L, Matucci-Cerinic M. Vitamin E gel reduces time of healing of digital ulcers in systemic sclerosis. Clin Exp Rheumatol. 2009 May-Jun;27(3 Suppl 54):51-4.
25. 25. de Souza RB, Macedo AR, Kuruma KA, Macedo PA, Borges CT. Pentoxyphylline in association with vitamin E reduces cutaneous fibrosis in systemic sclerosis. Clin Rheumatol 2009;28(10): 1207-12.
26. 26. Erre GL, De Muro P, Dellacâ P, Fenu P, Cherchi GM, Faedda R, Passiu G. Ilo-prost therapy acutely decreases oxidative stress in patients affected by systemic sclerosis. Clin Exp Rheumatol. 2008 Nov-Dec;26(6):1095-8.
27. 27. Plane F, Jacobs M, McManus D, Bruckdorfer KR. Probucol and other antioxidants. prevent the inhibition of endothelium-dependent relaxation by low density lipoproteins. Atherosclerosis. 1993; 103(1 ):73-9.