Şişman Jülide PUNAR, Eker Rukiye ÖMEROĞLU, Naci ÖNER, Kemal NİŞLİ, Zeynep AYDIN, Ayşegül TELCİ

Nonsteroid antiinflamatuvar ilaç kullanan jüvenil romatoid artritli hastalarda oksidan ve antioksidan sistemlerinin değerlendirilmesi

Giriş: Jüvenil romatoid artrit (JRA) çocukluk çağının en sık görülen, etyolojisi oldukça karmaşık olan romatolojik hastalığıdır. İnflamasyondaki doku hasarına katkıda bulunan serbest oksijen radikalleri (SOD) JRA etyopatogenezinde de önemli rol oynayabilir. Bu çalışmanın amacı non-steroidal antiinflamatuar ilaç (NSAİİ) tedavisi alan JRA’lı çocuklarda, SOD’u indirekt olarak gösteren biyokimyasal parametrelerin değerlendirilmesidir. Yöntem ve Gereçler: Çalışma JRA nedeniyle sadece NSAİİ alan 20 hasta ile aynı yaş grubundaki 20 sağlıklı çocukta yapılmıştır. Hasta ve kontrol grubunda süperoksit dismutaz (SOD), glutatyon peroksidaz (GPx), malondialdehit (MDA), Vitamin E, total sulfidril (T-SH) ve eritrosit deformabilitesi ölçülmüştür. Sonuçlar: Ortalama SOD aktivitesi, gruplar arasında istatistiksel olarak anlamlı bir fark göstermedi (p>0.05). Ortalama GSH, MDA, T-SH ve eritrosit deformibilitesi düzeyleri JRA’lı hastalarda daha düşük idi ve aradaki fark istatistiksel olarak anlamlı bulundu (p

Anahtar Kelimeler:

Anti-enflamatuvar ajanlar, steroid olmayan, Antioksidanlar, Artrit, jüvenil romatoid, Çocuk, Reaktif oksijen türleri

Oxidant and antioxidant system evaluation in children with juvenile rheumatoid arthritis, receiving non-steroidal antiinflammatory drugs

Background: Juvenile rheumatoid arthritis (JRA) is the most commonly diagnosed rheumatic disease in children which has exceedingly complex etiology. Oxidative free radicals (OFR) production at inflammation sites contributes to tissue damage and may also play a significant role in the pathogenesis of JRA. The aim of this study was to measure OFR indirectly by using biochemical assays in JRA children, receiving only non-steroidal anti-inflammatory drugs (NSAID). Material and Methods: Twenty JRA children, receiving NSAID and 20 healthy controls were included for the study. Superoksit dismutase (SOD), glutatyon peroxidase (GPx), malondialdehyde (MDA), vitamin E, total sulphidril (T-SH) and erythrocyte dephormability assays were measured. Results: SOD activity was not found to be different between patients and controls. Serum GPx, MDA, T-SH concentrations and erythrocyte dephormability index in patients were significantly lower than in healthy controls (p<0.01), whereas, plasma vitamin E concentrations of patients were found to be higher than those in controls (p<0.01). Discussion: This study showed that OFR did not increase, even slightly decrease in JRA children, receiving NSAID. The reason of this decrease OFR in these children may chronically used NSAID which blocked siklooxygenase enzyme.

Keywords:

Anti-Inflammatory Agents, Non-Steroidal, Antioxidants, Arthritis, Juvenile Rheumatoid, Child, Reactive Oxygen Species,

___

1.Cassidy TJ, Patty RE. Juvenile rheumatoid arthritis. In: Textbook of Pediatric Rheumatology. Third ed. Philadelphia: WB Saunders, 1995: 133-23.
2.Jones OY, Spencer CH, Bowyer SL, Dent PB, Gottlieb BS, Rabinovich CE. A multicenter case-control study on predictive factors distinguishing childhood leukemia from juvenile rheumatoid arthritis. Pediatrics 2000; 117:840-4.
3.Hsu CT, Lin YT, Yang YH, Chiang BL. Factors affecting clinical and therapeutic outcomes of patients with juvenile rheumatoid arthritis. Scand J Rheumatol 2004; 33:312-7.
4.Schneider R, Passo MH. Juvenile rheumatoid arthritis. Rheum Dis Clin North Am 2002; 28:503-30.
5.Ramos VA, Ramos PA, Dominguez MC. Role of oxidative stress in the maintenance of inflamation in patients with juvenile rheumatoid arthritis. J Pediatr (Rio J) 2000; 76:125-32.
6.Araujo V, Arnal C, Boronat M, Ruiz E, Dominguez C. Oxidant-antioxidant imbalance in blood of children with juvenile rheumatoid arthritis. Biofactors 1998; 8:155-9.
7.Southorn PA, Powis G. Free radicals medicine II: Involvement in human disease. Mayo Clin Proc 1988; 63:390-408.
8.Lunec J, Halloran SP, White AG, et al. Free radical oxidation (peroxidation) products in serum and sinovial fluid in rheumatoid artritis. J Rheumatol 1981; 8:233-45.
9.Southorn PA, Powis G. Free radicals in medicine I: Chemical nature and biologic reactions. Mayo Clin Proc 1988; 63:390-408.
10.Greenwald A. Oxygen radicals, inflammations and arthritis: Pathophysiological considerations and implications for treatment. Semin Arthritis Rheum 1991; 20:219-40.
11.Halliwell B. Oxygen radicals, nitric oxide and human infla-matory joint disease. Ann Rheum Dis 1995; 54:505-10.
12.Halliwell B, Gutteridge JMC. Oxygen toxicity, oxygen radicals, transitional metals and disease. Biochem J 1984; 219:1-14.
13.Kehrer JP. Free radicals as mediators of tissue injury and disease. Crit Rev Toxicol 1993; 23:21-48.
14- Igari T, Kaneda H, Horiuchi S, et al. A remarkable increase of superoxide dismutase activity in sinovial fluid of patients with rheumatoid arthritis. Clin Orthopaedics 1982; 162:282-7.
15.Marklund SL, Bjelle A, Elmqvist LG. Superoxide dismutase isoenzymes of the sinovial fluid in the rheumatoid arthritis and reactive arthritis. Ann Rheum Dis 1986; 45:847-51.
16.Sklowska M, Gromadzinska J, Biernacka M, et al. Vitamin E, thiobarbituric acid reactive substance concentrations and superoxide dismutase activity in the blood of children with juvenile rheumatoid arthritis. Clin Exp Rheumatol 1996; 14:433-9.
17.Hurd TC, Dashmahapatra K, Rush BF, et al. Red blood cell deformability in human and experimental sepsis. Arch Surg 1988; 123:217-20.
18.Ciufetti G, Ciacca A, Mercuri M, et al. Correlation between clinical and laboratory findings when the whole blood fil-terability rate is modified by ticlopidine in the treatment of rheumatoid arthritis. Br J Rheumatol 1989; 28:42-7.
19.Lau CS, Saniabadi AR, Belch JJF. Reduced red blood cell deformability in patients with rheumatoid vasculitis. Arthritis Rheum 1995; 38:248-53. 20.Langenfeld JE, Livingstone DH, Machiedo GW. Red cell deformability is an early indicator of infection. Surgery 1991; 110:398-404.
21.Merry P, Grootveld M, Lunec J, et al. Oxidative damage to lipids within inflamed human joint provides evidence of radical mediated hypoxi reperfusion injury. Am J Clin Nutr 1991; 53:362-9.
22.Rowley DA, Gutteridge JMC, Blake DR, et al. Lipid peroxidation in rheumatoid arthritis: Thiobarbituric acid reactive material and catalytic iron salts in synovial fluid from rheumatoid patients. Clin Sci 1984; 66:691-5.
23.Heliövaara M, Knekt P, Aho K, et al. Serum antioxidants and risk of rheumatoid arthritis. Ann Rheum Dis 1994; 53:51.
24.Benedetti FD, Pignatti P, Massa M, et al. Soluble tumour necrosis factor receptor levels reflect coagulation abnormalities in systemic juvenile chronic arthritis. Br Rheum 1997; 36: 581-8.
25.Hu ML. Measurement of protein tiol groups and glutation in plasma. Methods Enzymol 1994; 233:381-5.
26.Banford JC, Brown DH, Hazelton RA, et al. Altered thiol status in patient with rheumatoid arthritis. Rheumatol Int 1982; 2:107-11.
27.Zheng SX, Mouithys-Mickalad A, Deby-Dupont GP, Deby CM, Maroulis AP, Labasse AH, et al. In vitro study of the antioxidant properties of nimesulide and 4-OH nimesulide: effects on HRP- and luminol-dependent chemiluminescence produced by human chondrocytes. Osteoarthritis Cartilage. 2000; 8:419-25.
28.Maffei Facino R, Carini M, Aidini G, Şaibene L, Macci-occhi A. Antioxidant profile of nimesulide, indomethacin and diclofenac in phosphatidylcholine liposomes (PCL) as membrane model. Int J Tissue React 1993; 15:225-34.