Clinical Rheumatology

, Volume 33, Issue 11, pp 1557–1564

Correlation of oxidant status with oxidative tissue damage in patients with rheumatoid arthritis

  • Suhana Datta
  • Sunanda Kundu
  • Parasar Ghosh
  • Soumita De
  • Alakendu Ghosh
  • Mitali Chatterjee
Original Article

Abstract

Rheumatoid arthritis (RA) is a debilitating autoimmune disease whose etiology remains unknown, but studies have consistently implicated a plethora of inflammatory mechanisms culminating in chronic symmetric and erosive synovitis. Importantly, reactive oxygen species (ROS) have been attributed to directly contribute towards the destructive, proliferative synovitis evident in RA. Accordingly, this study aimed to establish whether the degree of oxidative stress and disease activity score (DAS28) correlated with the downstream effects of oxidative damage. The redox status of neutrophils sourced from synovial fluid (SF) was measured by flow cytometry in terms of total ROS and hydroxyl radicals. Among the molecular damage markers, protein carbonylation and lipid peroxidation were detected by spectrophotometry and S-nitrosothiols by fluorimetry. Neutrophils constituted the major cellular component of the SF of patients with RA and their levels of ROS and hydroxyl radicals correlated strongly with protein carbonylation and lipid peroxidation. However, all the oxidative damage markers correlated positively with DAS28. Taken together, in patients with RA, the strong correlation between levels of ROS and DAS28 with markers of oxidative damage suggests that measurement of oxidative stress could serve as a biomarker for monitoring disease severity in RA.

Keywords

Hydroxyl radicals Malonaldehyde Oxidative stress Protein carbonylation Rheumatoid arthritis S-nitrosothiols 

References

  1. 1.
    Filippin LI, Vercelino R, Marroni NP, Xavier RM (2008) Redox signaling and the inflammatory response in rheumatoid arthritis. Clin Exp Immunol 152:415–422PubMedCrossRefPubMedCentralGoogle Scholar
  2. 2.
    Mirshafiey A, Mohsenzadegan M (2008) The role of reactive oxygen species in immunopathogenesis of rheumatoid arthritis. Iran J Allergy Asthma Immunol 7:195–202PubMedGoogle Scholar
  3. 3.
    Goldsby RA, Kindt TJ, Osborne BA, Kuby J (2003) Leukocyte migration and inflammation. In: Immunology, 5th edn. WH Freeman, New York, pp 338–358Google Scholar
  4. 4.
    Dalle-Donne I, Rossi R, Colombo R, Giustarini D, Milzani A (2006) Biomarkers of oxidative damage in human disease. Clin Chem 52:601–623PubMedCrossRefGoogle Scholar
  5. 5.
    Forman HJ, Fukuto JM, Torres M (2004) Redox signaling: thiol chemistry defines which reactive oxygen and nitrogen species can act as second messengers. Am J Physiol Cell Physiol 287:C246–C256PubMedCrossRefGoogle Scholar
  6. 6.
    Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS et al (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315–324PubMedCrossRefGoogle Scholar
  7. 7.
    van der Linden MP, Batstra MR, Bakker-Jonges LE (2011) Towards a data-driven evaluation of the 2010 American College of Rheumatology/European League Against Rheumatism criteria for rheumatoid arthritis: is it sensible to look at levels of rheumatoid factor? Arthritis Rheum 63:1190–1199PubMedCrossRefGoogle Scholar
  8. 8.
    van Gestel AM, Haagsma CJ, van Riel PL (1998) Validation of rheumatoid arthritis improvement criteria that include simplified joint counts. Arthritis Rheum 41:1845–1850PubMedCrossRefGoogle Scholar
  9. 9.
    Mandal G, Wyllie S, Singh N, Sundar S, Fairlamb AH, Chatterjee M (2007) Increased levels of thiols protect antimony unresponsive Leishmania donovani field isolates against reactive oxygen species generated by trivalent antimony. Parasitology 134:1679–1687PubMedCrossRefPubMedCentralGoogle Scholar
  10. 10.
    Kundu S, Ghosh P, Datta S, Ghosh A, Chattopadhyay S, Chatterjee M (2012) Oxidative stress as a potential biomarker for determining disease activity in patients with Rheumatoid Arthritis. Free Radic Res 46:1482–1489PubMedCrossRefGoogle Scholar
  11. 11.
    Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275PubMedGoogle Scholar
  12. 12.
    Guilpain P, Chéreau C, Goulvestre C, Servettaz A, Montani D, Tamas N, Pagnoux C, Hachulla E, Weill B, Guillevin L, Mouthon L, Batteux F (2011) The oxidation induced by anti myeloperoxidase antibodies triggers fibrosis in microscopic polyangiitis. Eur Respir J 37:1503–1513PubMedCrossRefGoogle Scholar
  13. 13.
    Firuzi O, Fuksa L, Spadaro C, Bousová I, Riccieri V, Spadaro A, Petrucci R, Marrosu G, Saso L (2006) Oxidative stress parameters in different systemic rheumatic diseases. J Pharm Pharmacol 58:951–957PubMedCrossRefGoogle Scholar
  14. 14.
    Levine RL, Garland D, Oliver CN, Amici A, Climent I, Lenz AG, Shalfier S, Stadtman ER (1990) Determination of carbonyl content in oxidatively modified proteins. Methods Enzymol 186:464–478PubMedCrossRefGoogle Scholar
  15. 15.
    Mantle D, Falkous G, Walker D (1999) Quantification of protease activities in synovial fluid from rheumatoid and osteoarthritis cases: comparison with antioxidant and free radical damage markers. Clin Chim Acta 284:45–58PubMedCrossRefGoogle Scholar
  16. 16.
    Marzinzig M, Nussler AK, Stadler J, Marzinzig E, Barthen W, Nussler NC, Beger HG, Morris SM Jr, Brückner UB (1997) Improved methods to measure end products of nitric oxide in biological fluids: nitrite, nitrate, and S-nitrosothiols. Nitric Oxide 1:177–189PubMedCrossRefGoogle Scholar
  17. 17.
    Beuge JA, Aust SD (1978) Microsomal lipid peroxidation. Methods Enzymol 52:302–310CrossRefGoogle Scholar
  18. 18.
    Seven A, Güzel S, Aslan M, Hamuryudan V (2008) Lipid, protein, DNA oxidation and antioxidant status in rheumatoid arthritis. Clin Biochem 41:538–543PubMedCrossRefGoogle Scholar
  19. 19.
    Kundu S, Bala A, Ghosh P, Mukhopadhyay D, Mitra A, Sarkar A, Bauri AK, Ghosh A, Chattopadhyay S, Chatterjee M (2011) Attenuation of oxidative stress by allylpyrocatechol in synovial cellular infiltrate of patients with Rheumatoid Arthritis. Free Radic Res 45:518–526PubMedCrossRefGoogle Scholar
  20. 20.
    Santulli P, Borghese B, Lemaréchal H, Leconte M, Millischer AE, Batteux F, Chapron C, Borderie D (2013) Increased serum oxidative stress markers in women with uterine leiomyoma. 36. PLoS One 8:e72069PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    Stalmer JS, Singel DJ, Loscalzo J (1992) Biochemistry of nitric oxide and its redox-activated forms. Science 258:1898–1902CrossRefGoogle Scholar
  22. 22.
    Mylonas C, Kouretas D (1999) Lipid peroxidation and tissue damage. In Vivo 13:295–309PubMedGoogle Scholar
  23. 23.
    Halliwell B (2007) Free radicals in biology and medicine. Oxford University Press, New YorkGoogle Scholar
  24. 24.
    Dhiman M, Coronado YA, Vallejo CK, Petersen JR, Ejilemele A, Nuñez S, Zago MP, Spratt H, Garg NJ (2013) Innate immune responses and antioxidant/oxidant imbalance are major determinants of human Chagas disease. PLoS Negl Trop Dis 7:e2364PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    Chang D, Zhang X, Rong S, Sha Q, Liu P, Han T, Pan H (2013) Serum antioxidative enzymes levels and oxidative stress products in age-related cataract patients. Oxidative Med Cell Longev. doi:10.1155/2013/587826 Google Scholar
  26. 26.
    Bansal S, Chawla D, Siddarth M, Banerjee BD, Madhu SV, Tripathi AK (2013) A study on serum advanced glycation end products and its association with oxidative stress and paraoxonase activity in type 2 diabetic patients with vascular complications. Clin Biochem 46:109–114PubMedCrossRefGoogle Scholar
  27. 27.
    Yang XH, Liu X, Shang J, Liu HG, Xu YJ (2013) Correlation between the serum level of advanced oxidation protein products and the cognitive function in patients with obstructive sleep apnea hypopnea syndrome. Zhonghua Jie He He Hu Xi Za Zhi 36:274–279PubMedGoogle Scholar
  28. 28.
    Dalle-Donne I, Giustarini D, Colombo R, Rossi R, Milzani A (2003) Protein carbonylation in human diseases. Trends Mol Med 9:169–176PubMedCrossRefGoogle Scholar
  29. 29.
    Bhattacharya S, Mula S, Gamre S, Kamat JP, Bandyopadhyay SK, Chattopadhyay S (2007) Inhibitory property of Piper betel extract against photosensitization-induced damages to lipids and proteins. Food Chem 100:1474–1480CrossRefGoogle Scholar
  30. 30.
    Mahmoud AA, Ismail MA (2011) Serum protein carbonyl content, total thiol and nitric oxide in patients with rheumatoid arthritis. J Am Sci 7:683–686Google Scholar
  31. 31.
    Marin DP, Bolin AP, dos Santos RC, Curi R, Otton R (2010) Testosterone suppresses oxidative stress in human neutrophils. Cell Biochem Funct 28:394–402PubMedCrossRefGoogle Scholar
  32. 32.
    Roy S, Sannigrahi S, Vaddepalli RP, Ghosh B, Pusp P (2012) A novel combination of methotrexate and epigallocatechin attenuates the overexpression of pro-inflammatory cartilage cytokines and modulates antioxidant status in adjuvant arthritic rats. Inflammation 35:1435–1447PubMedCrossRefGoogle Scholar
  33. 33.
    Drafi F, Bauerova K, Kuncirova V, Ponist S, Mihalova D, Fedorova T, Harmatha J, Nosal R (2012) Pharmacological influence on processes of adjuvant arthritis: effect of the combination of an antioxidant active substance with methotrexate. Interdiscip Toxicol 5:84–91PubMedCrossRefPubMedCentralGoogle Scholar
  34. 34.
    Banji D, Pinnapureddy J, Banji OJ, Saidulu A, Hayath MS (2011) Synergistic activity of curcumin with methotrexate in ameliorating Freund’s complete adjuvant induced arthritis with reduced hepatotoxicity in experimental animals. Eur J Pharmacol 668:293–298PubMedCrossRefGoogle Scholar

Copyright information

© Clinical Rheumatology 2014

Authors and Affiliations

  • Suhana Datta
    • 1
  • Sunanda Kundu
    • 1
  • Parasar Ghosh
    • 2
  • Soumita De
    • 1
  • Alakendu Ghosh
    • 2
  • Mitali Chatterjee
    • 1
  1. 1.Department of PharmacologyInstitute of Post Graduate Medical Education and ResearchKolkataIndia
  2. 2.Department Rheumatology and Clinical ImmunologyInstitute of Post Graduate Medical Education and ResearchKolkataIndia

Personalised recommendations