Osteoartritin Patogenezinde Rolü Olan Oksidatif Stres ve İnflamasyon Üzerine Hyalüronik Asidin Etkisi

Year 2010, Volume: 11 Issue: 1, 1 - 7, 01.04.2010

Sibel Koçar Çelik Ahmet Kahraman Gökhan Maralcan

Abstract

Keywords

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Osteoartritin Patogenezinde Rolü Olan Oksidatif Stres ve İnflamasyon Üzerine Hyalüronik Asidin Etkisi

Abstract

Amaç: Osteoartrit (OA), deformite ve sakatlığa kadar giden bulgu ve semptomlara neden olarak hayatın yaşam kalitesini düşürmektedir. Hastanın yaşam kalitesini artırmak amacıyla uygulanan birçok tedavi semptomlara yöneliktir ve semptomatik iyileşme sağlarlar. Asıl kıkırdak yapımını azaltan ve yapımını artıran kıkırdak koruyucu tedaviye ihtiyaç vardır. Konroprotektif ilaçlar, hastalığını gerilemesini ve progresyonunun yavaşlamasını sağlarlar. Bu amaçla hyalüronik asit (HA ) preparatları kullanılmaktadır. Bu çalışmada osteoartritli (OA) hastalara hyalüronik asit (HA) uygulamasının OA’in patogenezinde rolü olan inflamasyon ve oksidatif stres üzerine etkilerini belirlemeyi amaçladık. Gereç ve yöntemler: Diz OA’li hastalara (n=8) intraartiküler olarak 3 doz HA uygulandı. HA uygulanmadan önce (kontrol grubu) ve 3. dozunun uygulanmasından sonra (tedavi grubu) enjektör ile eklem sıvısı elde edildi. Kontrol grubu ve tedavi grubu eklem sıvılarında lipit peroksidasyon ürünü olan malondialdehit düzeyi (MDA) , anti oksidan kapasiteyi gösteren redükte glutatyon (GSH) ve protein sülfidril (SH) grupları ile infilamatuar procesin göstergesi olarak tümör nekrozis faktör-α (TNF- α) düzeyleri ve protein karbonil içeriği çalışıldı. Bulgular: Tedavi grubunda MDA (p < 0.05), karbonil (p < 0.01) ve TNF-α (p < 0.01) düzeylerinin anlamlı olarak azaldığı, GSH (p < 0.05) düzeylerinin anlamlı olarak arttığı gözlendi. Protein SH gruplarının düzeylerinde de hafif artma saptandı. Ancak istatistiksel olarak anlamlı değildi (p > 0.05). Sonuç: Biz HA tedavisinin, eklem sıvısında azalmış MDA, karbonil ve TNF-α düzeyleri, artmış SH ve GSH düzeyleri ile ilişkili olarak OA’in patogenezinde pozitif etkileri olduğu düşünüyoruz

Keywords

Osteoartrit, hyalüronik asit, inflamasyon, oksidatif stres

References

• Şendur F, Berkit IK, Osteoarthrıitis rehabilitation. Turkiye Klinikleri J Int Med Sci. 2006, 2: 44-51.
• Cooper C. Osteoarthritis and related disorders- Epidemiology. In: Klippel JH, Dieppe PA (Ed): Rheumatology. Philadelphia: Mosby 1998. p.1-8.
• Kallman DA, Wigley FM, Scott WW. New radiographic grading scales for osteoarthritis of the hand: reliability for determining prevalance and prog- ression. Arthritis Rheum, 1989; 32: 1584–1591.
• Martin JA, Buckwalter JA. Roles of articular cartilage aging and chondrocyte senescence in the pathogenesis of osteoarthritis. Lowa Orthop. J, 2001; 21: 1–7.
• Altman R, Asch E, Bloch D. The American College Rheumatology criteria for the classification and reporting of osteoarthrtits of the knee. Arthritis Rheum, 1986; 29: 1039–1049.
• Dozin B, Malpeli M, Camardella L. Cancedda R, Pietrangelo A. Response of young, aged and osteoarthritic human articular chondrocytes to inflammatory cytokines: molecular and cellular aspects. Matrix Biol, 2002; 21: 449–459.
• Dieppe P. Osteoarthritis: Clinical features and diagnostic problems. In: Klippel JH, Dieppe P, eds. Rheumatology. Colchester: Mosley Year Books, 1994. p.1–16.
• Melchiorri C, Meliconi R, Frizziero L, Silvestri T, Pulsatelli L, Mazzetti I, et al. Enhanced and coordinated in vivo expression of inflammatory cytokines and NOS by chondrocytes from patients with osteoarthritis. Arthritis Rheum, 1998; 41: 2165– 2174.
• Fujisawa T, Hattori T, Takahashi K, Kuboki T, Yamashita A, Takiga-wa M. Cyclic mechanical stres induces extracellular matrix degradation in cultured chondrocytes via gene expression of matrix metalloproteinases and interleukin–1. J.Biochem (Tokyo), 1999; 125: 966–975.
• Honda K, Ohno S, Tanimoto K, Ijuin C, Tanaka N, Doi T, et al..The effects of high magnitude cyclic ten- sile load on cartilage matrix metabolism in cultured chondrocytes. Eur. J. Cell Biol, 2000; 79: 601–609.
• Lee DA, Frean SP, Lees P, Bader DL. Dynamic mechanical comp-ression influences nitric oxide production by articular chondrocytes seeded in agarose. Biochem. Biophy. Res. Commun, 1998; 251: 580–585.
• Miyagi I, Kikuchi H, Hamanishi C, Tanaka S. Autodestruction of the articular cartilage and free radical mediators. J. Lab. Clin. Med, 1998; 131: 146– 150.
• Smith MD, Triantafillau S, Parker A, Youssef PP, Coleman M. Syno-vial membrane inflammation and cytokine production in patients with early osteoarthritis. J Rheumatol, 1997; 24: 365–371.
• Haklar U, Yüksel M, Velioğlu A, Turkmen M, Haklar G, Yalçin A.S. Oxygen radicals and nitric oxide levels in chondral or meniscal lesions or both. Clin Orthop Relat Res, 2002; 403: 135–142.
• Felson DT. The course of osteoarthritis and factors that affect it. Rheum Dis Clin North Am, 1993; 19: 607–615.
• Altman R, Asch E, Bloch D, Bole G, Borenstein D, Brandt K, et al. Development of criteria for the classification and reporting of osteoarthritis: Classification of osteoarthritis of the knee. Arthritis Rheum, 1986; 29: 1039–1049.
• Lo YY, Conquer JA, Grinstein S, Cruz TF. Interleukin–1β induction of c-fos and collagenase expression in articular chondrocytes: Involvement of ROS. J Cell Biochem, 1998; 69: 19–29.
• Henrotin Y, Deby-Dupont G, Deby C, Franchimont P, Emerit I. Active oxygen species, articular inflammation and cartilage damage. In: Eme-rit I. Chance B. Eds. Free Radicals and Aging. Basel: Birkhaüser verlag, 1992. p. 308–322.
• Henrotin YE, Bruckner P, Pujol J-PL. The role of reactive oxygen species in homeostasis and degradation of cartilage. Osteoarthritis Cartilage, 2003; 11: 747–755.
• Borderıe D, Hıllıquın P, Hernvann A, Lemarechal H, Menkes CJ, Ekındjıan OG. Apoptosis induced by nitric oxide is associated with nuclear p53 protein expression in cultured osteoarthritic synoviocytes. Osteoarthritis Cartilage, 1999;7: 203–213.
• Blanco FJ, Ochs RL, Schwarz H And Lotz M. Chondrocyte apopto-sis induced by nitric oxide. Am. J. Pathol, 1995; 146: 75–85.
• Blanco FJ, Guitian R, Vazquez-Martul E, De Toro F.J. and Galdo F. Osteoarthritis chondrocytes die by apoptosis. A possible pathway for os-teoarthritis pathology. Arthritis Rheum, 1998; 41: 284–289.
• Hashimoto S, Ochs RL, Komiya S. And Lotz M. Linkage of chond-rocyte apoptosis and cartilage degradation in human osteoarthritis. Arthritis Rheum, 1998; 41: 1632–1638.
• Blanco FJ and Lotz M. IL–1 induced nitric oxide inhibits chondrocyte proliferation via PG E2. Exp. Cell Res, 1995; 218: 319–325.
• Clancy RM, Leszczynska-Piziak J, Abramson S. Nitric oxide, an en-dotelial cell relaxation factor, inhibits neutrophil superoxide anion production via a direct action on the NADPH oxidase. J Clin Invest, 1992; 90: 1116–1121.
• Taskiran D, Stefanovic-Racic M, Georgescu H And Evans C. Nitric oxide mediates suppression of cartilage proteoglycan synthesis by interleu-kin–1. Biochem. Biophys. Res Commun, 1994; 200: 142– 148.
• Murrel GA, Jang D And Williams RJ. Nitric oxide activates metallo-protease enzymes in articular cartilage. Biochem. Biophys. Res. Commun, 1995; 206: 15–21.
• Gür S, Dabak KT, Concervative treatment in cartilage. Turkiye Klinikleri J Surg Med Sci, 2006; 2: 57-60.
• Campo MG, Avenoso A, Campo S, Ferlazzo AM, Altavilla D, Calat-roni A. Efficacy of treatment with glycosaminoglycans on experimental collo-gen- induced arthritis in rats. Arthritis Res Ther, 2003; 5: 122–131.
• Levine RL, Garland D, Oliver CN, Amici A, Climent L, Lenz AG, et al. Determination of carbonyl content in oxidatively modified proteins. Methods Enzymol, 1990;186: 464–478.
• Okhawa H, Ohishi N, Yagi K. Assay for lipid peroxidase in animal tissues by thiobarbituric acid reaction. Anal Biochem, 1979; 95: 351–358.
• Beutler E, Robson MJ, Buttenwieser E. The glutathione instability of drug sensitive red cells. j Lab Clin Med, 1957; 49: 84.
• Koster JF, Biemond P, Swaak JG. Intracellular and extracellular sulphydryl levels in rheumatoid arthritis. Ann Rheum Dis., 1986; 45: 44–46.
• Akkuş İ. Serbest radikaller ve fizyopatolojik etkileri, Mimoza yayınları, Kuzucular Ofset, Konya, 1995. p. 32-41.
• Chapman ML, Rubin BR, Gracy RW. Increased carbonyl content of proteins in synovial fluid from patients with rheumatoid arthritis. J Rheumatol, 1989; 16: 15–18.
• Moreland LW. Intra-articular hyaluronan (hyaluronic acid) and hylans fort he treatment of osteoarthritis:mechanisms of action. Arthritis Res Ther, 2003; 5: 54–67.
• Xu P, Zhang Y, Yao J. Study on the effect of sodium hyaluronate intra-articular injection on the treatment of knee osteoarthritis. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi, 2005; 19: 210-214.
• Grigolo B, Roseti L, Fiorini M, Facchini A. Enhanced lipid peroxidation in synoviocytes from patients with osteoarthritis. J Rheumatol. 2003; 30: 345-347.
• Carlo MD Jr, Loeser RF. Increased oxidative stres with aging reduces chondrocyte survival: correlation with intracellular glutathione levels. Arthritis Rheum. 2003; 48: 3419-3430.
• Sezgin M, Demirel AC, Karaca C, Ortancil O, Ulkar GB, Kanik A, et.al. Does hyaluronan affect inflammatory cytokines in knee osteoarthri-tis? Rheumatol Int, 2005; 25: 264-249.