Evaluation of serum nitric oxide level and its relationship with disease activity parameters in patients with rheumatoid arthritis

Abstract

Aim: Nitric oxide (NO) is a molecule known to play a role in many physiological and pathological events in the body. It is thought to play an active role in inflammation. Rheumatoid arthritis (RA) is the most common chronic inflammatory autoimmune disease worldwide. In this study, we aimed to evaluate the serum NO levels of RA patients and their relation with parameters that are indicators of disease activity. Material and Method: Thirty patients with RA (7 males/ 23 females, mean age 48.80±7.88 years old) and 30 healthy control groups were included in the study. Both groups were compared with erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), anti cyclic citrullinated peptide antibody (anti CCP) and serum NO levels and clinically with Visual Analog Scale (VAS), Disease Activity Score-28 (DAS-28) and Health Assessment Questionnaire (HAQ) scales. Results: ESR, CRP and NO levels in the patient group were significantly higher than the control group (p<0.05). When the patient group was classified as active and inactive group (active disease: DAS-28> 3.2, inactive disease DAS-28 <3.2) according to DAS-28 scores, there was no significant difference in serum NO levels between the two groups. Serum NO levels of the patient group were not correlated with clinical (VAS, DAS-28) and laboratory markers (ESR, CRP, RF, Anti CCP) of disease activity. Conclusion: In this study, we found that serum NO levels in RA patients increased significantly compared to the healthy control group. However, increased serum NO levels in RA patients were not associated with laboratory and clinical disease activity parameters.

Keywords

• Nitric oxide
• Rheumatoid arthritis
• Disease Activity Score-28 (DAS-28)
• Health Assessment Questionnaire (HAQ)

References

1. 1. van’t Hof RJ, Hocking L, Wright PK, Ralston SH. Nitric oxide is a mediator of apoptosis in the rheumatoid joint. Rheumatology 2000;39(9):1004–1008.
2. 2. Headland SE, Jones HR, Norling LV, et al. Neutrophil-derived microvesicles enter cartilage and protect the joint in inflammatory arthritis. Sci Transl Med 2015;25:7(315):315ra190.
3. 3. Zhang Q, Dehaini D, Zhang Y, et al. Neutrophil membrane-coated nanoparticles inhibit synovial inflammation and alleviate joint damage in inflammatory arthritis Nanotechnol 2018;13(12):1182−1190.
4. 4. Nathan C, Xie QW. Regulation of biosynthesis of nitric oxide. J Biol Chem 1994;269:13725-13728.
5. 5. Nathan C, Xie QW. Nitric oxide Synthesis: Roles, tolls and controls. Cell 1994;78:915-918.
6. 6. Moncada S, Palmer RM, Higgs EA. Nitric oxide: Physiology, pathophysiology and pharmacology. Pharmol Rev 1991;43:109-142.
7. 7. Beltrán B, Mathur A, Duchen MR, Erusalimsky JD, Moncada S. The effect of nitric oxide on cell respiration: A key to understanding its role in cell survival or death. Proc Natl Acad Sci USA 2000;97: 14602-14607.
8. 8. Yeo J, Lee YM, Lee J,et al. Nitric Oxide-Scavenging Nanogel for Treating Rheumatoid Arthritis. Nano Lett 2019;9:19(10):6716-6724.

9. 9. Nagy G, Koncz A, Telarico T, et al. Central role of nitric oxide in the pathogenesis of rheumatoid arthritis and systemic lupus erythematosus. Arthritis Res Ther 2010;12(3):210.
10. 10. Kolios G, Valatas V, Ward SG. Nitric oxide in inflammatory bowel disease: a universal Messenger in an unsolved puzzle. Immunology 2004;113(4):427−37.
11. 11. Ali AM, Habeeb RA, El-Azizi NO, Khattab DA, Abo-Shady RA, Elkabarity RH. Higher nitric oxide levels are associated with disease activity inEgyptian rheumatoid arthritis patients. Rev Bras Reumatol 2014;54(6):446–451.
12. 12. Mazzetti B, Grigolo L, Pulsatelli P,et al. Differential roles of nitric oxide and oxygen radicals in chondrocytes affected by osteoarthritis and rheumatoid arthritis. Clin Sci (Lond.) 2001;101(6):593–599.
13. 13. Pham TN, Rahman P, Tobin YM, et al. Elevated serum nitric oxide levels in patients with inflammatory arthritis associated with co-expression of inducible nitric oxide synthase and protein kinase C-eta in peripheral blood monocyte-derived macrophages. J Rheumatol 2003;30:2529-2534.
14. 14. Stichtenoth DO, Frolich JC. Nitric oxide and inflammatory joint diseases. Br J Rheumatol 1998;37:246-57.
15. 15. Cortas NK, Wakid NW. Determination of inorganic nitrate in serum and urine by a kinetic cadmium-reduction method. Clin Chem 1990;36(8):1440-1443.
16. 16. Farrell AJ, DR, Palmar RMJ. Increased concentrations of nitrite in synovial fl uid and serum samples suggest increased nitric oxide synthesis in rheumatic diseases. Ann Rheum Dis 1992;51:1219-1222.
17. 17. Spiller F, Oliveira Formiga R, Fernandes da Silva Coimbra J, Alves-Filho JC, Cunha TM, Cunha FQ. Targeting nitric oxide as a key modulator of sepsis, arthritis and pain. Nitric Oxide 2019;1:89:32-40.
18. 18. Laskin DL, Heck DE, Laskin JD. Role of inflammatory cytokines and nitric oxide in hepatic and pulmonary toxicity. Toxicology Letters 1998;102:289-293.
19. 19. Kolb H, Kolb-Bachofen V. Nitric oxide in autoimmune disease: Cytotoxic or regulatory mediator? Immunol Today 1998;19: 556-561.
20. 20. Al-Nimer MSM, Al-Obaidi SAH, Al-Dulaimi KS. Serum nitric oxide and peroxynitrite levels in adult sero-positive rheumatoid arthritis treated with disease modifying antirheumatic drugs: a preliminary report. Turkish Journal of Medical Sciences 2010;40(2):191-197.
21. 21. Nathan C. Indicuble nitric oxide synthase: What difference does it make? J Clin Invest 1997;100:2417-2423.
22. 22. McCartney-francis N, Allen BJ, Mizel DE: Suppression of arthritis by an inhibitor of nitrice oxide synthase. J Exp Med 1993;178:749-754.
23. 23. Khallaf HA, Nosair NAA, Alashkar DS, Abdella DHM. Assessment of serum nitrite level in patients with rheumatoid arthritis. Tanta Medical Journal 2016;44(1):12.
24. 24. Taysi S, Umudum Z, Sari RA, Kuskay S, Bakan N. Nitric oxide level and superoxide dismutase activity in serum of patients with rheumatoid arthritis. The Pain Clinic 2003;15(4):429-434.
25. 25. Ersoy Y, Ozerol E, Baysal O, et al. Serum nitrate and nitrite levels in patients with rheumatoid arthritis, ankylosing spondylitis, and osteoarthritis. Ann Rheum Dis 2002;61(1):76-78.
26. 26. Veselinovic M, Barudzic N, Vuletic M, et al. Oxidative stress in rheumatoid arthritis patients: relationship to diseases activity. Mol Cell Biochem 2014; 391:225–232.
27. 27. Onur O, Akinci AS, Akbiyik F, Unsal I. Elevated levels of nitrate in rheumatoid arthritis. Rheumatol Int 2001;20:154-158.
28. 28. Choi JW. Nitric oxide production is increased in patients with rheumatoid arthritis but does not correlate with laboratory parameters of disease activity. Clin Chim Acta 2003;336:83-87.
29. 29. Güzel S, Seven A, Güzel EC, Hamuryudan V. Nitric oxide and superoxide dismutase in rheumatoid arthritis: correlation with disease activity. Turkish J Family Med Primary Care 2012; 6:7–12.
30. 30. Nagy G, Clark JM, Buzas E, et al. Nitric oxide production of T lymphocytes is increased in rheumatoid arthritis. Immunol Lett 2008;118(1):55-8.