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The effect of therapeutic agents on serum copper levels and serum oxidase activities in the rat adjuvant model compared to analogous results from studies of rheumatoid arthritis in humans

  • W. E. Smith
  • D. H. Brown
  • J. Dunlop
  • R. Hazelton
  • R. D. Sturrock
  • A. J. Lewis
Part of the Inflammation: Mechanisms and Treatment book series (FTIN, volume 4)

Abstract

Among the many biochemical changes observed in rheumatoid arthritis and other inflammatory disorders has been a pronounced elevation in serum copper1–3. A similar rise in serum copper has also been observed in the adjuvant arthritic rat4–7. Since ceruloplasmin is the major copper-carrying protein in serum, it seemed likely that there should be a relationship between total serum copper and ceruloplasmin in the diseased and normal states. Recent studies would support this8,9, but there are also claims that non-ceruloplasmin copper may be the major source of additional copper in rheumatoid arthritis3,10. Furthermore, in studies of cancer in animals, the ratio of the amount to the activity of ceruloplasmin, the main oxidase in serum, varies with the severity of the disease11. We decided to investigate the copper-ceruloplasmin relationship in adjuvant arthritis in the rat and to relate this to copper levels in patients with rheumatoid arthritis and normal human controls. These studies were intended to give some insight into the activity of serum copper as well as the amount of the copper and consequently the relationship of these parameters to drug therapies was also studied.

Keywords

Rheumatoid Arthritis Copper Level Adjuvant Arthritis Cuprous Oxide Serum Copper 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Niedermeir, W. (1965). Concentration and chemical state of copper in synovial fluid and blood serum of patients with rheumatoid arthritis. Ann. Rheum. Dis., 24, 544CrossRefGoogle Scholar
  2. 2.
    Plantin, L. O. and Strandberg, P. O. (1965). Whole blood concentrations of copper and zinc in rheumatoid arthritis studied by activation analysis. Acta Rheum. Scand., 11, 30PubMedGoogle Scholar
  3. 3.
    Lorber, A., Cutler, L. S. and Chang, C. C. (1968). Serum levels in rheumatoid arthritis: relationship of elevated copper to protein alterations. Arthritis Rheum., 11,65PubMedCrossRefGoogle Scholar
  4. 4.
    Gralla, E. J. and Wiseman, E. H. (1968). The adjuvant arthritic rat: Inflammatory parameters during the development and regression of gross lesions. Proc. Soc. Exp. Biol. Med., 128, 493PubMedGoogle Scholar
  5. 5.
    Jacques, R., Maijer, H., Riesterer, L. and Rüegg, M. (1971). Mast cell count in the peritoneal fluid of rats with adjuvant-induced polyarthritis. Pharmacology, 5, 81CrossRefGoogle Scholar
  6. 6.
    Hirschelmann, R., Bekemeier, H. and Stelzner, A. (1977). Acute-phase reactants of the blood in rat adjuvant arthritis as indicators of the degree of inflammation and of’specific’ and unspecific anti-inflammatory effects. Z. Rheumatol., 36, 305PubMedGoogle Scholar
  7. 7.
    Lewis, A.J., Cottney,J., TeapeJ., Dunlop,J., Smith, W. E. and Brown,D.H. (1980). Copper and its involvement in the inflammatory process. Eur. J. Rheumatol. Inflamm. (In press)Google Scholar
  8. 8.
    Scudder, P.R., Al-Timmini, D., McMurray, W., White, A. G., Zoob, B.C. and Dormandy, T. L. (1978). Serum copper and related variables in rheumatoid arthritis. Ann. Rheum. Dis., 37, 67PubMedCrossRefGoogle Scholar
  9. 9.
    Brown, D.H., Buchanan, W.W., El-Ghobarey, A.F., Smith, W.E. and Teape, J. (1979). Serum copper and its relationship to clinical symptoms in rheumatoid arthritis. Ann. Rheum. Dis., 38,174PubMedCrossRefGoogle Scholar
  10. 10.
    Pruzanski, W., Russel, M. L., Gordon, D. A. and Ogryzlo, M. A. (1973). Serum and synovial fluid proteins in rheumatoid arthritis and degenerative joint disease. Am. J. Med. Sci., 265,485CrossRefGoogle Scholar
  11. 11.
    Linder, M. C., Bryant, R. R., Lunn, S., Scott, L. E. and Moor, J. E. (1979). Ceruloplasmin elevation and synthesis in rats with transplantable tumours. Enzyme, 24, 85PubMedGoogle Scholar
  12. 12.
    Boiano, J.M., Menden, E.E., Murthy, L. and Petering, H. G. (1977). Modification of a p-phenylene diamine oxidase method to permit non automated ceruloplasmin determinations in batches of rat serum or plasma. Anal. Lett., 10,197CrossRefGoogle Scholar
  13. 13.
    Teape, J., Kamel, H., Brown, D.H., Ottaway, J. M. and Smith, W. E. (1979). An evaluation of the use of electrophoresis and carbon furnace atomic absorption spectrometry to determine the copper level in separated serum protein fractions. Clin. Chim. Acta., 94,1PubMedCrossRefGoogle Scholar
  14. 14.
    Lewis, A., Brown, D. H., Dunlop, J. and Smith, W. E. (unpublished results)Google Scholar
  15. 15.
    Dunlop, J. and Hazelton, R. (unpublished results)Google Scholar
  16. 16.
    Crichton, R. R. (1973). Ferritin Structure and Bonding. 17, 67CrossRefGoogle Scholar
  17. 17.
    Ryden, L. and Björk, I. (1976). Reinvestigation of some physiochemical and chemical properties of human ceruloplasmin (Ferroxidase). Biochemistry, 15, 3411PubMedCrossRefGoogle Scholar
  18. 18.
    Frieden, E. and McKee, D. J. (1971). Binding oftransition metalions by ceruloplasmin. Biochemistry, 10,3880Google Scholar
  19. 19.
    Brown, D.H., Dunlop, J., Smith, W.E., Teape, J., Cottney, J. and Lewis, A.J. (1979). Copper distribution following administration of cuprous oxide to rats and guinea pigs. Agents Actions, 9,Google Scholar
  20. 20.
    Blake, D. R., Eastham, E. J., and Thomson, M. (1980). Serum and synovial fluid ferritin in rheumatoid arthritis. This volume, Chap. 67Google Scholar

Copyright information

© MTP Press Limited 1980

Authors and Affiliations

  • W. E. Smith
    • 1
  • D. H. Brown
    • 1
  • J. Dunlop
    • 1
  • R. Hazelton
    • 1
  • R. D. Sturrock
    • 1
  • A. J. Lewis
    • 1
  1. 1.UK

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