Agents and Actions

, Volume 25, Issue 1–2, pp 146–155 | Cite as

Changes in zinc, copper and selenium status during adjuvant-induced arthritis in rats

  • J. Nève
  • J. Fontaine
  • A. Peretz
  • J. P. Famaey
Immunosuppression and Inflammations


Trace elements such as zinc, copper and selenium are involved in the pathogenesis of inflammatory diseases. In order to obtain more information about the overall movements of these minerals during the evolution of an experimental chronic inflammatory process, trace element levels were determined in five body compartments of the rat at several time intervals after induction of adjuvant arthritis. Rapid and significant changes in plasma zinc and copper levels and in liver zinc levels were observed. These modifications occurred as early as those in biochemical parameters of inflammation such as serum fibrinogen and ceruloplasmin, and preceded the appearance of any clinical symptom of the disease. Inverse correlations were found between plasma zinc levels and these two biochemical indices. Other modifications in trace element levels were observed two weeks after disease induction, the most important being a considerable increase in liver copper levels. Although food intake of affected animals decreased with the progression of the disease, there was no evidence of depletion in zinc and copper levels over the study period. A redistribution of body zinc between different biological compartments (mainly plasma and liver) occurred simultaneously with an accumulation of copper in several organs. The decreasing selenium status of animals was not clearly related to the inflammatory process.


Selenium Zinc Level Copper Level Adjuvant Arthritis Plasma Zinc 
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  1. [1]
    M. W. Whitehouse and W. R. Walker,Copper and inflammation. Agents and Actions8, 85–90 (1978).CrossRefPubMedGoogle Scholar
  2. [2]
    A. J. Lewis, W. E. Smith and D. H. Brown,A comparison of the anti-inflammatory activities of copper complexes in different models of inflammation. InTrace Elements in the Pathogenesis and Treatment of Inflammation. (Eds. K. D. Rainsford, K. Brune and M. W. Whitehouse) pp. 327–338, Birkhäuser, Basel 1981.Google Scholar
  3. [3]
    J. R. S. Sorenson,Copper complexes, an unique class of antiarthritic drugs. InProgress in Medicinal Chemistry, vol. 15 (Eds. G. P. Ellis and G. B. West) pp. 211–260, Elsevier, North Holland 1978.Google Scholar
  4. [4]
    R. Milanino and G. P. Velo,Multiple actions of copper in control of inflammation: studies in copper deficient rats. InTrace Elements in the Pathogenesis and Treatment of Inflammation. (Eds. K. D. Rainsford, K. Brune and M. W. Whitehouse) pp. 209–230, Birkhäuser, Basel 1981.Google Scholar
  5. [5]
    R. Milanino, E. Passarella and G. P. Velo,Adjuvant arthritis in young copper deficient rats. Agents and Actions8, 623–628 (1978).CrossRefPubMedGoogle Scholar
  6. [6]
    A. J. Lewis,The role of copper in inflammatory disorders. Agents and Actions15, 513–519 (1984).CrossRefPubMedGoogle Scholar
  7. [7]
    S. A. Al-Nagdy, A. K. Khattab, M. M. Abd El Fattah,The levels of some inorganic elements in the sera of rheumatic children. J. Trop. Med. Hyg.75, 237–243 (1972).PubMedGoogle Scholar
  8. [8]
    A. A. R. Youssef, B. Wood and D. N. Baron,Serum copper, a marker of disease activity in rheumatoid arthritis. J. Clin. Pathol.36, 14–17 (1983).PubMedGoogle Scholar
  9. [9]
    J. R. J. Sorenson and J. J. Ditomaso,The significance of increased plasma and serum copper concentrations in rheumatoid arthritis. Ann. Rheum. Dis.35, 186–188 (1976).PubMedGoogle Scholar
  10. [10]
    M. Kekki, P. Koskelo and A. Lassus,Serum ceruloplasminbound copper and non-ceruloplasmin copper in uncomplicated psoriasis. J. Invest. Dermatol.47, 159–163 (1966).PubMedGoogle Scholar
  11. [11]
    A. Conforti, L. Franco, R. Milanino, A. Totorizzo and G. P. Velo,Copper metabolism during acute inflammation: studies on liver and serum copper concentrations in normal and inflamed rats. Br. J. Pharmac.79, 45–52 (1983).Google Scholar
  12. [12]
    D. S. Karabelas,Copper metabolism in the adjuvant-induced arthritic rats. Univ. Microfilms Ann. Arbor Mich, Order no 72–31, 092. From Diss. Abstr. Int.13 1972–33, 2776 (1972).Google Scholar
  13. [13]
    V. Kishore, N. Latman, D. W. Roberts, J. B. Barnett and J. R. J. Sorenson,Effects of nutritional copper deficiency on adjuvant arthritis and immonocompetence in the rat. Agents and Actions14, 274–282 (1984).CrossRefPubMedGoogle Scholar
  14. [14]
    J. Sadique, S. Somasundaram and S. Hazeema Begum,The influence of antiarthritic medicinal plants on trace elements metabolism in adjuvant arthritic rats. Acta Pharmacol. Toxicol.59, suppl. 7, 406–409 (1986).Google Scholar
  15. [15]
    R. Milanino, A. Conforti, L. Franco M. Marrella and G. Velo,Copper and inflammation — a possible rationale for the pharmacological manipulation of inflammatory disorders. Agents and Actions16, 504–513 (1985).CrossRefPubMedGoogle Scholar
  16. [16]
    R. Milanino, A. Cassini, A. Conforti, L. Franco, M. Marella, V. Moretti and G. P. Velo,Copper and zinc status during acute inflammation: studies on blood, liver and kidneys metal levels in normal and inflamed rats. Agents and Actions19, 213–223 (1986).CrossRefGoogle Scholar
  17. [17]
    B. F. Feldman, C. L. Keen, J. J. Kaneko and T. B. Farver,Anemia of inflammatory disease in the dog: measurements of hepatic superoxide disease, hepatic non heme iron, copper and zinc. Am. J. Vet. Res.42, 1114–1117 (1980).Google Scholar
  18. [18]
    R. E. Lee and W. E. M. Lanos,Cofactors in the biosynthesis of prostaglandins F 1 and F 2 Biochem. biophys. Acta260, 203–211 (1972).PubMedGoogle Scholar
  19. [19]
    J. C. Ludwig and M. Chvapil,Effects of metal ions on lysosomes. InTrace Elements in the Pathogenesis and Treatment of Inflammation. (Eds. K. D. Rainsford, K. Brune and M. W. Whitehouse) pp. 65–84, Birkhäuser Basel, 1981.Google Scholar
  20. [20]
    U. Weser and L. M. Schubotz,Catalytic reaction of copper complexes with superoxide. InTrace Elements in the pathogenesis and Treatment of Inflammation. (Eds. K. D. Rainsford, K. Brune and M. W. White house). pp. 103–120, Birkhäuser, Basel 1981.Google Scholar
  21. [21]
    R. Millanino, E. Passarella and G. P. Velo,Copper and the inflammatory process. InAdvances in Inflammation Research, vol. 1. (Eds. G. Weissmann, B. Samuelsson and R. Paoletti) pp. 281–291, Raven Press, New York 1979.Google Scholar
  22. [22]
    M. C. Powanda, G. L. Cockerell and R. S. Pekarek,Amino acid and zinc movement in relation to protein synthesis early in inflammation. Am. J. Physiol.225, 399–401 (1973).PubMedGoogle Scholar
  23. [23]
    M. S. Pekarek and G. W. Evans,Effects of acute infection and endotoxemia on zinc absorption in the rat. Proc. Soc. Exp. Biol. Med.150, 755–758 (1975).PubMedGoogle Scholar
  24. [24]
    M. C. Powanda, K. A. Bostian, R. E. Dinterman, N. G. Fee, J. P. Fowler, E. C. Hauer and J. D. White,Phagocytosis and the metabolic sequelae of infection. J. Reticuloendothelial Soc.27, 67–82 (1980).Google Scholar
  25. [25]
    S. Balogh, A. F. El Ghobarey, G. S. Fell, P. H. Brown, J. Dunlop and W. C. Dick,Plasma zinc and its relation to clinical symptoms and drug treatment in rheumatoid arthri tis. Ann. Rheum. Dis.39, 329–331 (1980).PubMedGoogle Scholar
  26. [26]
    M. A. Cimmino, L. Parre, M. Cutolo, T. Valente and S. Rovipa,Zinc concentrations in rheumatoid arthritis and psoriatic arthritis. Are they relevant to the inflammatory process? Scand. J. Rheumatol.15, 403–406 (1987).Google Scholar
  27. [27]
    P. A. Simkin,Oral Zinc sulfate in rheumatoid arthritis. Lancet II, 539–542 (1976).CrossRefGoogle Scholar
  28. [28]
    F. Fernandez-Madrid, A. S. Prasad and B. Oberleas,Effect of zinc deficiency on collagen metabolism. J. Lab. Clin. Med.78, 853–863 (1981).Google Scholar
  29. [29]
    B. C. Starcher, C. H. Hill and J. C. Madaras,Effect of zinc deficiency on bone collagenase and bone turnover. J. Nutr.,110, 2095–2102 (1980).PubMedGoogle Scholar
  30. [30]
    S. N. Meydani and J. Dupont,Effect of zinc deficiency on prostaglandin synthesis in different organs of the rat. J. Nutr.112, 1098–1103 (1982).PubMedGoogle Scholar
  31. [31]
    P. J. Fraker, M. E. Gershwin, R. A. Good and A. S. Prasad,Interrelationship between zinc and immune function. Fed. Proc.45, 1474–1478 (1986).PubMedGoogle Scholar
  32. [32]
    P. C. Bragt and I. L. Bonta,Role of trace elements in hepatic changes during inflammatory conditions. In:Trace Elements in the Pathogenesis and Treatment of Inflammation. (Eds. K. D. Rainsford, K. Brune and M. W. White house) pp. 231–239, Birkhäuser, Basel 1981.Google Scholar
  33. [33]
    M. J. Parnham and E. Graf,Seleno-organic compounds and the therapy of hydroperoxide-linked pathological conditions. Biochem. Pharmacol.36, 3095–3102 (1987).CrossRefPubMedGoogle Scholar
  34. [34]
    M. J. Parnham, J. Winkelmann and S. Leyck,Macrophage, lymphocyte and chronic inflammatory responses in selenium deficient rodents. Association with decreased glutathione peroxidase activity. Int. J. Immunopharmac.5, 455–461 (1983).CrossRefGoogle Scholar
  35. [35]
    U. Tarp, K. Overvad, J. C. Hansen and E. B. Thorling,Low selenium level in severe rheumatoid arthritis. Scand. J. Rheumatol.14, 97–101 (1985).PubMedGoogle Scholar
  36. [36]
    B. Akesson, U. Johannson, P. A. Ockerman, S. Portisson, A. Akesson and H. Swantesson,Selenium status in patients with juvenile chronic arthritis. InTrace Element Analytical Chemistry in Medicine and Biology, vol. 3. (Eds. P. Bratter and P. Schramel) pp. 167–174, W. de Gruyter, Berlin 1984.Google Scholar
  37. [37]
    A. Peretz, J. Neve, F. Vertongen and J. P. Famaey,Selenium status in relation to clinical parameters and corticosteroid treatment in rheumatoid arthritis. J. Rheumatol.14, 1104–1107 (1987).PubMedGoogle Scholar
  38. [38]
    C. Larson, J. M. Gorman, A. M. Becker,Automated immunoprecipitation system for protein in body fluids-further advances. In:Advances in Automated Analysis, vol. 4.Technicon Int. Congress, pp. 15–17. Mediad. Inc. Tarrytown, NY 1973.Google Scholar
  39. [39]
    A. Von Clauss,Gerinnungphysiologische Snellmethode zur Bestimmung des Fibrinogens. Acta Hematol.,17, 237–246 (1957).Google Scholar
  40. [40]
    J. B. Dawson and B. E. Walker,Direct determination of zinc in whole blood, plasma and urine by atomic absorption spectrophotometry, Clin. Chim. Acta26, 465–475 (1969).CrossRefPubMedGoogle Scholar
  41. [41]
    P. Scudder, J. Stocks and T. L. Dormandy,The relationship between erythrocyte superoxide dismutase activity and erythrocyte copper levels in patients with rheumatoid arthritis. Clin. Chim. Acta69, 397–403 (1976).CrossRefPubMedGoogle Scholar
  42. [42]
    J. Nève and L. Molle,Direct determination of selenium in human serum by graphite furnace atomic absorption spectroscopy. Improvements due to oxygen ashing in graphite tube and Zeeman effect background correction. Acta Pharmacol. Toxicol.59, 606–609 (1986).Google Scholar
  43. [43]
    J. Nève, S. Chamart and L. Molle,Optimization of a direct procedure for the determination of selenium in plasma and erythrocytes using Zeeman effect atomic absorption spectroscopy. In:Trace Element Analytical Chemistry in Medicine and Biology, vol. 4 (Eds. P. Bratter and P. Schramel), pp. 349–359, W. de Gruyter, Berlin 1987.Google Scholar
  44. [44]
    J. Nève, M. Hanocq, L. Molle and G. LefebvreStudy of some systematic errors during the dtermination of the total selenium and some of its ionic species in biological materials. The Analyst107, 934–941 (1982).CrossRefPubMedGoogle Scholar
  45. [45]
    E. Berman,Determination of copper in serum and tissues by atomic absorption spectroscopy. Atom. Absorpt. Newslett.4, 296 (1965).Google Scholar
  46. [46]
    G. W. Snedecor and W. G. Cochran,Statistical Methods. 6th ed., Iowa State University Press, Ames 1967.Google Scholar
  47. [47]
    A. J. Lewis, R. P. Carlson and J. Chang,Experimental models of inflammation. In: ThePharmacology of Inflammation, Handbook of Inflammation, vol. 5. (Eds. I.L. Bonta, M. A. Broy and M. J. Parnham), pp. 371–397, Elsevier Science Publishing, 1985.Google Scholar
  48. [48]
    W. B. Robinson,Nutrition and rheumatic diseases. InTextbook of Rheumatology, vol. 1. (Eds. W. N. Kelley, E. D. Harris, S. Ruddy and C. B. Sledge) pp. 337–349, W. B. Saunders, Philadelphia, London, Toronto 1981.Google Scholar
  49. [49]
    R. J. CousinsAbsorption, transport and hepatic metabolism of copper and zinc: special reference to metallothionein and ceruloplasmin. Physiol. Rev.65, 238–309 (1985).PubMedGoogle Scholar
  50. [50]
    P. T. Bailey, F. B. Abeles E. C. Hauer and C. A. Mapes,Intracerebroventricular activity of leucocytic endogenous mediators (LEM) in the rat. Proc. Soc. Exp. Biol. Med.53, 419–425 (1976).Google Scholar
  51. [51]
    K. C. Klasing,Effects of inflammatory agents and interleukin-1 on iron and zinc metabolism. Am. J. Physiol.247, R901-R904 (1984).PubMedGoogle Scholar
  52. [52]
    M. L. Failla and R. J. Cousins,Zinc uptake by isolated rat liver parenchymal cells. Biochem. Biophys. Acta.,538, 435–444 (1978).PubMedGoogle Scholar
  53. [53]
    R. A. Di Silvestro and R. J. Cousins,Mediation of endotoxin-induced changes in zinc metabolism in rats, Am. J. Physiol.247, E436-E441 (1984).PubMedGoogle Scholar
  54. [54]
    M. C. Powanda,Systemic alterations in metal metabolism during inflammation as part of an integrated response to inflammation. InTrace Elements in the Pathogenesis and Treatment of Inflammation (Eds K. D. Rainsford, K. Brune and M. W. White house) pp. 65–84, Birkhäuser, Basel 1981.Google Scholar
  55. [55]
    E. L. Litchi M. Turner, J. H. Henzel and M. S. Deweese,Wound fluid zinc levels during tissue repair. Am. J. Surg.121, 665–667 (1980).Google Scholar
  56. [56]
    R. A. Bonebrake, J. J. Mc Call, G. G. Hunder and H. F. Polley,Zinc accumulation in synovial fluid. Mayo Clin. Proc.47, 746–750 (1972).PubMedGoogle Scholar
  57. [57]
    A. Peretz, J. Nève, F. Vertongen and J. P. Famaey,Synovial fluid copper, zinc and selenium in relation to inflammatory parameters in rheumatic diseases. InBiology of Copper Complexes. (Ed. J. R. J. Sorenson) pp. 583–589, Humana Press Inc. Clifton, New Jersey 1987.Google Scholar
  58. [58]
    J. R. J. Sorenson,Mean serum copper, magnesium and zinc concentrations in active rheumatoid and other degenerative connective tissue diseases. InTrace Elements in Environmental Health, vol. 11. (Ed. D. D. Hemphill) pp. 15–21, University of Missouri, Columbia 1977.Google Scholar
  59. [59]
    J. Nève, A. Peretz, F. Vertongen, J. Fontaine, J. P. Famaey and L. Molle,Variations du zinc dans les maladies rhumatismales. InLe Zinc en Médecine et Biologie. (Ed. A. Favier, J. Arnaud and H. Faure) pp. 237–243. Editions Médicales Internationales, Paris, 1987.Google Scholar
  60. [60]
    A. Conforti, L. Franco, R. Milanino and G. P. Velo,Copper and ceruloplasmin concentrations during the acute inflammatory process in the rat. Agents and Actions12, 303–307 (1982).CrossRefPubMedGoogle Scholar
  61. [61]
    A. Conforti, L. Franco, R. Milanino, R. Milanino and G. P. Velo,Serum copper concentrations and ceruloplasmin activity during carrageenan foot oedema in rat. Br. J. Pharmac.72, 137P-138P (1981).Google Scholar

Copyright information

© Birkhäuser Verlag 1988

Authors and Affiliations

  • J. Nève
    • 1
  • J. Fontaine
    • 2
  • A. Peretz
    • 3
  • J. P. Famaey
    • 3
  1. 1.Toxicology and Bioanalytical Chemistry Unit, Institute of PharmacyUniversité Libre de BruxellesBrusselsBelgium
  2. 2.Laboratory of Pharmacology, Institute of PharmacyUniversité Libre de BruxellesBruxellesBelgium
  3. 3.Department of Rheumatology and Physical MedicineUniversity Hospital Saint-PierreSaint-PierreBelgium

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