Skip to main content
NCBI home page
Annals of the Rheumatic Diseases logoLink to Annals of the Rheumatic Diseases
. 1986 Oct;45(10):839–846. doi: 10.1136/ard.45.10.839

Early and late changes in sulphydryl group and copper protein concentrations and activities during drug treatment with aurothiomalate and auranofin.

K J Rae, C N Mackay, C J McNeil, D H Brown, W E Smith, D Lewis, H A Capell
PMCID: PMC1002006  PMID: 3098194

Abstract

Superoxide dismutase activity (SOD), plasma and lysate thiol concentrations (PSH and LSH), and caeruloplasmin oxidase activity (CP) reflect the underlying reduction-oxidation imbalance associated with rheumatoid arthritis (RA), and are believed to be involved in the protection of the cell against free radical activity. The early and late changes in these parameters have been observed and compared with standard clinical and biochemical assessments of disease activity in 90 patients with active RA, randomly assigned to receive either sodium aurothiomalate, auranofin, or auranofin placebo. An index based on clinical criteria was used to identify patients as responders or non-responders after 24 weeks of therapy. In the first six weeks of treatment a change in SOD activity and LSH concentration in a direction away from controls was followed by a return towards control levels in responders only. This suggests that in RA evidence of clinical improvement induced by gold drugs is preceded by an initial biochemical response in an inflammatory direction. The extracellular parameters PSH and CP did not show the same early response, but PSH levels in responders showed a slower change towards normal values, though at no time were values obtained that might suggest a complete remission. Thus the intracellular parameters appear to reflect an early effect of the drugs on cells which may possibly be of use in predicting the outcome of therapy, whereas the extracellular parameters provide confirmatory evidence for an eventual improvement.

Full text

PDF
839

Selected References

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

  1. Banford J. C., Brown D. H., Hazelton R. A., McNeil C. J., Smith W. E., Sturrock R. D. Altered thiol status in patients with rheumatoid arthritis. Rheumatol Int. 1982;2(3):107–111. doi: 10.1007/BF00541162. [DOI] [PubMed] [Google Scholar]
  2. Banford J. C., Brown D. H., Hazelton R. A., McNeil C. J., Sturrock R. D., Smith W. E. Serum copper and erythrocyte superoxide dismutase in rheumatoid arthritis. Ann Rheum Dis. 1982 Oct;41(5):458–462. doi: 10.1136/ard.41.5.458. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Berglöf F. E., Berglöf K., Walz D. T. Auranofin: an oral chrysotherapeutic agent for the treatment of rheumatoid arthritis. J Rheumatol. 1978 Spring;5(1):68–74. [PubMed] [Google Scholar]
  4. Brown D. H., Buchanan W. W., el-Ghobarey A. F., Smith W. E., Teape J. Serum copper and its relationship to clinical symptoms in rheumatoid arthritis. Ann Rheum Dis. 1979 Apr;38(2):174–176. doi: 10.1136/ard.38.2.174. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. ELLMAN G. L. Tissue sulfhydryl groups. Arch Biochem Biophys. 1959 May;82(1):70–77. doi: 10.1016/0003-9861(59)90090-6. [DOI] [PubMed] [Google Scholar]
  6. Finkelstein A. E., Walz D. T., Batista V., Mizraji M., Roisman F., Misher A. Auranofin. New oral gold compound for treatment of rheumatoid arthritis. Ann Rheum Dis. 1976 Jun;35(3):251–257. doi: 10.1136/ard.35.3.251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Goldstein I. M., Kaplan H. B., Edelson H. S., Weissmann G. Ceruloplasmin. A scavenger of superoxide anion radicals. J Biol Chem. 1979 May 25;254(10):4040–4045. [PubMed] [Google Scholar]
  8. Hall N. C., Gillan A. H. Effects of antirheumatic drugs on protein sulphydryl reactivity of human serum. J Pharm Pharmacol. 1979 Oct;31(10):676–680. doi: 10.1111/j.2042-7158.1979.tb13627.x. [DOI] [PubMed] [Google Scholar]
  9. Mallya R. K., Mace B. E. The assessment of disease activity in rheumatoid arthritis using a multivariate analysis. Rheumatol Rehabil. 1981 Feb 1;20(1):14–17. doi: 10.1093/rheumatology/20.1.14. [DOI] [PubMed] [Google Scholar]
  10. McNeil C. J., Banford J. C., Brown D. H., Smith W. E. A relationship between thiols and the superoxide ion. FEBS Lett. 1981 Oct 12;133(1):175–177. doi: 10.1016/0014-5793(81)80498-x. [DOI] [PubMed] [Google Scholar]
  11. Misra H. P., Fridovich I. Superoxide dismutase: a photochemical augmentation assay. Arch Biochem Biophys. 1977 May;181(1):308–312. doi: 10.1016/0003-9861(77)90509-4. [DOI] [PubMed] [Google Scholar]
  12. Pickup M. E., Dixon J. S., Bird H. A. On the effects of antirheumatic drugs on protein sulphydryl reactivity in human serum. J Pharm Pharmacol. 1980 Apr;32(4):301–302. doi: 10.1111/j.2042-7158.1980.tb12920.x. [DOI] [PubMed] [Google Scholar]
  13. Rister M., Bauermeister K., Gravert U., Gladtke E. Superoxide-dismutase deficiency in rheumatoid arthritis. Lancet. 1978 May 20;1(8073):1094–1094. doi: 10.1016/s0140-6736(78)90933-9. [DOI] [PubMed] [Google Scholar]
  14. Ritchie D. M., Boyle J. A., McInnes J. M., Jasani M. K., Dalakos T. G., Grieveson P., Buchanan W. W. Clinical studies with an articular index for the assessment of joint tenderness in patients with rheumatoid arthritis. Q J Med. 1968 Jul;37(147):393–406. [PubMed] [Google Scholar]
  15. Salin M. L., McCord J. M. Free radicals and inflammation. Protection of phagocytosine leukocytes by superoxide dismutase. J Clin Invest. 1975 Nov;56(5):1319–1323. doi: 10.1172/JCI108208. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Scudder P. R., Al-Timimi D., McMurray W., White A. G., Zoob B. C., Dormandy T. L. Serum copper and related variables in rheumatoid arthritis. Ann Rheum Dis. 1978 Feb;37(1):67–70. doi: 10.1136/ard.37.1.67. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Youssef A. A., Baron D. N. Leucocyte superoxide dismutase in rheumatoid arthritis. Ann Rheum Dis. 1983 Oct;42(5):558–562. doi: 10.1136/ard.42.5.558. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Annals of the Rheumatic Diseases are provided here courtesy of BMJ Publishing Group

RESOURCES