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Annals of the Rheumatic Diseases logoLink to Annals of the Rheumatic Diseases
. 1991 Feb;50(2):81–86. doi: 10.1136/ard.50.2.81

Chain breaking antioxidant status in rheumatoid arthritis: clinical and laboratory correlates.

R D Situnayake 1, D I Thurnham 1, S Kootathep 1, S Chirico 1, J Lunec 1, M Davis 1, B McConkey 1
PMCID: PMC1004342  PMID: 1998395

Abstract

The ability of fresh sera to resist attack by peroxyl radicals (TRAP) was found to be significantly lower in 20 patients with rheumatoid arthritis (RA) than in 20 healthy controls, consistent with the existence of a redox stress in RA imposed by inflammation. TRAP values in RA varied inversely with a combination of visual analogue pain scale, duration of early morning stiffness, grip strength, and articular index (reflecting inflammatory activity) using multiple linear regression analysis. The concentration of the antioxidant vitamin ascorbic acid was lower in RA plasma and the oxidation-reduction equilibrium of ascorbic acid was disturbed, giving further support to the existence of a redox stress. The major determinant of TRAP in vitro was found to be serum uric acid in RA and serum vitamin E in controls. Serum urate concentration in RA correlated inversely with oxidative changes in serum albumin and IgG. It is suggested that serum urate might have an antioxidant role under certain conditions by limiting free radical induced oxidative changes to protein during inflammation.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Agudelo C. A., Turner R. A., Panetti M., Pisko E. Does hyperuricemia protect from rheumatoid inflammation? A clinical study. Arthritis Rheum. 1984 Apr;27(4):443–448. doi: 10.1002/art.1780270412. [DOI] [PubMed] [Google Scholar]
  2. Ames B. N., Cathcart R., Schwiers E., Hochstein P. Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis. Proc Natl Acad Sci U S A. 1981 Nov;78(11):6858–6862. doi: 10.1073/pnas.78.11.6858. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Babior B. M. Oxygen-dependent microbial killing by phagocytes (second of two parts). N Engl J Med. 1978 Mar 30;298(13):721–725. doi: 10.1056/NEJM197803302981305. [DOI] [PubMed] [Google Scholar]
  4. Biemond P., Swaak A. J., Koster J. F. Protective factors against oxygen free radicals and hydrogen peroxide in rheumatoid arthritis synovial fluid. Arthritis Rheum. 1984 Jul;27(7):760–765. doi: 10.1002/art.1780270706. [DOI] [PubMed] [Google Scholar]
  5. Biemond P., Swaak A. J., Penders J. M., Beindorff C. M., Koster J. F. Superoxide production by polymorphonuclear leucocytes in rheumatoid arthritis and osteoarthritis: in vivo inhibition by the antirheumatic drug piroxicam due to interference with the activation of the NADPH-oxidase. Ann Rheum Dis. 1986 Mar;45(3):249–255. doi: 10.1136/ard.45.3.249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Blake D. R., Merry P., Unsworth J., Kidd B. L., Outhwaite J. M., Ballard R., Morris C. J., Gray L., Lunec J. Hypoxic-reperfusion injury in the inflamed human joint. Lancet. 1989 Feb 11;1(8633):289–293. doi: 10.1016/s0140-6736(89)91305-6. [DOI] [PubMed] [Google Scholar]
  7. Burton G. W., Webb A., Ingold K. U. A mild, rapid, and efficient method of lipid extraction for use in determining vitamin E/lipid ratios. Lipids. 1985 Jan;20(1):29–39. doi: 10.1007/BF02534359. [DOI] [PubMed] [Google Scholar]
  8. Cawood P., Wickens D. G., Iversen S. A., Braganza J. M., Dormandy T. L. The nature of diene conjugation in human serum, bile and duodenal juice. FEBS Lett. 1983 Oct 17;162(2):239–243. doi: 10.1016/0014-5793(83)80763-7. [DOI] [PubMed] [Google Scholar]
  9. Corongiu F. P., Milia A. An improved and simple method for determining diene conjugation in autoxidized polyunsaturated fatty acids. Chem Biol Interact. 1983 Jun;44(3):289–297. doi: 10.1016/0009-2797(83)90056-x. [DOI] [PubMed] [Google Scholar]
  10. Cranfield L. M., Gollan J. L., White A. G., Dormandy T. L. Serum antioxidant activity in normal and abnormal subjects. Ann Clin Biochem. 1979 Nov;16(6):299–306. doi: 10.1177/000456327901600181. [DOI] [PubMed] [Google Scholar]
  11. Doba T., Burton G. W., Ingold K. U. Antioxidant and co-antioxidant activity of vitamin C. The effect of vitamin C, either alone or in the presence of vitamin E or a water-soluble vitamin E analogue, upon the peroxidation of aqueous multilamellar phospholipid liposomes. Biochim Biophys Acta. 1985 Jul 9;835(2):298–303. doi: 10.1016/0005-2760(85)90285-1. [DOI] [PubMed] [Google Scholar]
  12. Egan R. W., Paxton J., Kuehl F. A., Jr Mechanism for irreversible self-deactivation of prostaglandin synthetase. J Biol Chem. 1976 Dec 10;251(23):7329–7335. [PubMed] [Google Scholar]
  13. Fairbank J., Ridgway L., Griffin J., Wickens D., Singer A., Dormandy T. L. Octadeca-9-11-dienoic acid in diagnosis of cervical intraepithelial neoplasia. Lancet. 1988 Aug 6;2(8606):329–330. doi: 10.1016/s0140-6736(88)92375-6. [DOI] [PubMed] [Google Scholar]
  14. Greenwald R. A., Moy W. W. Effect of oxygen-derived free radicals on hyaluronic acid. Arthritis Rheum. 1980 Apr;23(4):455–463. doi: 10.1002/art.1780230408. [DOI] [PubMed] [Google Scholar]
  15. Gutteridge J. M. Antioxidant properties of the proteins caeruloplasmin, albumin and transferrin. A study of their activity in serum and synovial fluid from patients with rheumatoid arthritis. Biochim Biophys Acta. 1986 Jan 30;869(2):119–127. doi: 10.1016/0167-4838(86)90286-4. [DOI] [PubMed] [Google Scholar]
  16. Hall N. D., Maslen C. L., Blake D. R. The oxidation of serum sulph-hydryl groups by hydrogen peroxide secreted by stimulated phagocytic cells in rheumatoid arthritis. Rheumatol Int. 1984;4(1):35–38. doi: 10.1007/BF00683883. [DOI] [PubMed] [Google Scholar]
  17. Halliwell B., Grootveld M. The measurement of free radical reactions in humans. Some thoughts for future experimentation. FEBS Lett. 1987 Mar 9;213(1):9–14. doi: 10.1016/0014-5793(87)81455-2. [DOI] [PubMed] [Google Scholar]
  18. Halliwell B. Production of superoxide, hydrogen peroxide and hydroxyl radicals by phagocytic cells: a cause of chronic inflammatory disease? Cell Biol Int Rep. 1982 Jun;6(6):529–542. doi: 10.1016/0309-1651(82)90175-8. [DOI] [PubMed] [Google Scholar]
  19. Halliwell B., Wasil M., Grootveld M. Biologically significant scavenging of the myeloperoxidase-derived oxidant hypochlorous acid by ascorbic acid. Implications for antioxidant protection in the inflamed rheumatoid joint. FEBS Lett. 1987 Mar 9;213(1):15–17. doi: 10.1016/0014-5793(87)81456-4. [DOI] [PubMed] [Google Scholar]
  20. Hewitt S. D., Lunec J., Morris C. J., Blake D. R. Effect of free radical altered IgG on allergic inflammation. Ann Rheum Dis. 1987 Nov;46(11):866–874. doi: 10.1136/ard.46.11.866. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hughes P. E., Hunter W. J., Tove S. B. Biohydrogenation of unsaturated fatty acids. Purification and properties of cis-9,trans-11-octadecadienoate reductase. J Biol Chem. 1982 Apr 10;257(7):3643–3649. [PubMed] [Google Scholar]
  22. Iversen S. A., Cawood P., Dormandy T. L. A method for the measurement of a diene-conjugated derivative of linoleic acid, 18:2(9,11), in serum phospholipid, and possible origins. Ann Clin Biochem. 1985 Mar;22(Pt 2):137–140. doi: 10.1177/000456328502200204. [DOI] [PubMed] [Google Scholar]
  23. Koster J. F., Biemond P., Swaak A. J. Intracellular and extracellular sulphydryl levels in rheumatoid arthritis. Ann Rheum Dis. 1986 Jan;45(1):44–46. doi: 10.1136/ard.45.1.44. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Lunec J., Blake D. R., McCleary S. J., Brailsford S., Bacon P. A. Self-perpetuating mechanisms of immunoglobulin G aggregation in rheumatoid inflammation. J Clin Invest. 1985 Dec;76(6):2084–2090. doi: 10.1172/JCI112212. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Lunec J., Halloran S. P., White A. G., Dormandy T. L. Free-radical oxidation (peroxidation) products in serum and synovial fluid in rheumatoid arthritis. J Rheumatol. 1981 Mar-Apr;8(2):233–245. [PubMed] [Google Scholar]
  26. MCCARTY D. J., Jr THE PENDULUM OF PROGRESS IN GOUT: FROM CRYSTALS TO HYPERURICEMIA AND BACK. Arthritis Rheum. 1964 Oct;7:534–541. doi: 10.1002/art.1780070509. [DOI] [PubMed] [Google Scholar]
  27. Packer J. E., Slater T. F., Willson R. L. Direct observation of a free radical interaction between vitamin E and vitamin C. Nature. 1979 Apr 19;278(5706):737–738. doi: 10.1038/278737a0. [DOI] [PubMed] [Google Scholar]
  28. Rowley D. A., Halliwell B. Formation of hydroxyl radicals from hydrogen peroxide and iron salts by superoxide- and ascorbate-dependent mechanisms: relevance to the pathology of rheumatoid disease. Clin Sci (Lond) 1983 Jun;64(6):649–653. doi: 10.1042/cs0640649. [DOI] [PubMed] [Google Scholar]
  29. Rowley D., Gutteridge J. M., Blake D., Farr M., Halliwell B. Lipid peroxidation in rheumatoid arthritis: thiobarbituric acid-reactive material and catalytic iron salts in synovial fluid from rheumatoid patients. Clin Sci (Lond) 1984 Jun;66(6):691–695. doi: 10.1042/cs0660691. [DOI] [PubMed] [Google Scholar]
  30. Sevanian A., Davies K. J., Hochstein P. Conservation of vitamin C by uric acid in blood. J Free Radic Biol Med. 1985;1(2):117–124. doi: 10.1016/0748-5514(85)90015-7. [DOI] [PubMed] [Google Scholar]
  31. Situnayake R. D., Crump B. J., Zezulka A. V., Davis M., McConkey B., Thurnham D. I. Measurement of conjugated diene lipids by derivative spectroscopy in heptane extracts of plasma. Ann Clin Biochem. 1990 May;27(Pt 3):258–266. doi: 10.1177/000456329002700313. [DOI] [PubMed] [Google Scholar]
  32. Stocks J., Gutteridge J. M., Sharp R. J., Dormandy T. L. The inhibition of lipid autoxidation by human serum and its relation to serum proteins and alpha-tocopherol. Clin Sci Mol Med. 1974 Sep;47(3):223–233. doi: 10.1042/cs0470223. [DOI] [PubMed] [Google Scholar]
  33. Thompson S., Smith M. T. Measurement of the diene conjugated form of linoleic acid in plasma by high performance liquid chromatography: a questionable non-invasive assay of free radical activity? Chem Biol Interact. 1985 Nov;55(3):357–366. doi: 10.1016/s0009-2797(85)80142-3. [DOI] [PubMed] [Google Scholar]
  34. Thurnham D. I., Davies J. A., Crump B. J., Situnayake R. D., Davis M. The use of different lipids to express serum tocopherol: lipid ratios for the measurement of vitamin E status. Ann Clin Biochem. 1986 Sep;23(Pt 5):514–520. doi: 10.1177/000456328602300505. [DOI] [PubMed] [Google Scholar]
  35. Wayner D. D., Burton G. W., Ingold K. U., Barclay L. R., Locke S. J. The relative contributions of vitamin E, urate, ascorbate and proteins to the total peroxyl radical-trapping antioxidant activity of human blood plasma. Biochim Biophys Acta. 1987 Jun 22;924(3):408–419. doi: 10.1016/0304-4165(87)90155-3. [DOI] [PubMed] [Google Scholar]
  36. Wayner D. D., Burton G. W., Ingold K. U., Barclay L. R., Locke S. J. The relative contributions of vitamin E, urate, ascorbate and proteins to the total peroxyl radical-trapping antioxidant activity of human blood plasma. Biochim Biophys Acta. 1987 Jun 22;924(3):408–419. doi: 10.1016/0304-4165(87)90155-3. [DOI] [PubMed] [Google Scholar]
  37. Wayner D. D., Burton G. W., Ingold K. U., Locke S. Quantitative measurement of the total, peroxyl radical-trapping antioxidant capability of human blood plasma by controlled peroxidation. The important contribution made by plasma proteins. FEBS Lett. 1985 Jul 22;187(1):33–37. doi: 10.1016/0014-5793(85)81208-4. [DOI] [PubMed] [Google Scholar]

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