Skip to main content
SpringerLink
Log in

Modulation of exudate inflammation parameters in rat carrageenan-induced granuloma by modification of exudate iron levels

  • Allergy, Histamine and Kinins
  • Published:
Agents and Actions Aims and scope Submit manuscript

Abstract

We have used the carrageenan-induced pouch-granuloma in rats to investigate how changes in low-molecular-mass iron chelate levels in the exudate, induced by iron loading (iron-dextran) or chelation (desferrioxamine) influence cellular and systemic inflammatory parameters.

In the iron-treated group we observed a rapid decrease in the number of leukocytes and exudate volume; there was also an increase in ferritin iron and low-molecular-mass iron chelates, and on the eighth day a systemic response. In the desferrioxamine-treated group we detected a decrease in low-molecular-mass iron chelates, ferritin iron, and an increase in the number of leukocytes. We describe the protective effects of desferrioxamine against the deleterious effects of ferrous iron and relate this to its chelating and scavenging activity.

The results suggest that the levels of low-molecular-mass iron chelates modulate the inflammatory response, possibly through their contribution to the oxygen free radical generation, which is responsible for the cell membrane damage and subsequently its death. The modulatory action of iron-dextran and desferrioxamine support our hypothesis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. P. Puig-Parellada and J. M. Planas,Synovial fluid degradation induced by free radicals. In vitro action of several free radical scavengers and anti-inflammatory drugs. Biochem. Pharmacol.27, 535–537 (1978).

    Article  PubMed  Google Scholar 

  2. F. A. Jr. Kuehl, J. L. Humes, M. L. Torchiana, E. A. Ham and R. W. Egan,Oxygen-centered radicals in inflammatory processes. Adv. Inflamm. Res.1, 419–430 (1979).

    Google Scholar 

  3. J. M. C. Gutteridge, D. A. Rowley and B. Halliwell,Superoxide-dependent formation of hydroxyl radicals in the presence of iron salts. Detection of “free” iron in biological systems by using bleomycin-dependent degradation of DNA. Biochem. J.199, 263–265 (1981).

    PubMed  Google Scholar 

  4. P. Biemond, H. G. van Eyk, A. J. G. Swaak and J. F. Koster,Iron mobilization from ferritin by superoxide derived from stimulated polymorphonuclear leukocytes. Possible mechanism in inflammation diseases. J. Clin. Invest.73, 1576–1579 (1984).

    PubMed  Google Scholar 

  5. B. Halliwell, J. M. C. Gutteridge and D. Blake,Metal ions and oxygen radical reactions in human inflammatory joint disease. Phil. Trans. R. Soc. Lond. B311, 659–671 (1985).

    Google Scholar 

  6. J. M. C. Gutteridge,Iron promoters of the Fenton reaction and lipid peroxidation can be released from haemoglobin by peroxides. FEBS Lett.201, 291–295 (1986).

    Article  PubMed  Google Scholar 

  7. D. R. Blake, N. D. Hall, P. A. Bacon, P. A. Dieppe, B. Halliwell and J. M. C. Gutteridge,The importance of iron in rheumatoid diseases.Lancet ii, 1142–1144 (1981).

    Article  Google Scholar 

  8. M. C. Linder and H. N. Munro,Assay of tissue ferritin. Anal. Biochem.48, 266–278 (1972).

    Article  PubMed  Google Scholar 

  9. T. L. Dormandy,Caeruloplasmin: acute-phase antioxidant.In Trace elements on the pathogenesis and treatment of inflammation. (Ed. K. D. Rainsford, K. Brune and M. W. Whitehouse) pp. 185–197, Birkhäuser Verlag, Basel 1981.

    Google Scholar 

  10. S. Osaki, D. A. Johnson and E. Frieden,The possible significance of the ferrous oxidase activity of ceruloplasmin in normal human serum. J. Biol. Chem.241, 2746–2751 (1966).

    PubMed  Google Scholar 

  11. I. M. Goldstein, H. B. Kaplan, H. S. Edelson and G. Weisseman,Ceruloplasmin-A scavenger of superoxide anion radicals. J. Biol. Chem.254, 4040–4045 (1979).

    PubMed  Google Scholar 

  12. M. Fukuhara and S. Tsurufuji,The effect of locally injected anti-inflammatory drugs on the carrageenin granuloma in rats. Biochem. Pharmacol.18, 475–484 (1969).

    Article  PubMed  Google Scholar 

  13. J. W. Drysdale and W. N. M. Ramsay,The separation of ferritin and haemosiderin for studies in the metabolism of iron. Biochem. J.95, 282–288 (1965).

    PubMed  Google Scholar 

  14. F. W. Jr. Sunderman and S. Nomoto,Measurement of human serum ceruloplasmin by its p-phenylenediamine oxidase activity. Clin. Chem.16, 903–910 (1970).

    PubMed  Google Scholar 

  15. J. Ball, J. A. Chapman and K. D. Muirden,The uptake of iron in rabbit synovial tissue following intra-articular injection of iron dextran. A light and electron microscope study. J. Cell Biol.22, 351–364 (1964).

    Google Scholar 

  16. B. S. van Asbeck, J. J. M. Marx, A. Struyvenberg, J. H. van Kats and J. Verhoef,Effect of iron (III) in the presence of various ligands on the phagocytic and metabolic activity of human polymorphonuclear leukocytes. J. Immunol.132, 851–856 (1984).

    PubMed  Google Scholar 

  17. A. G. Mowat, T. F. Disney and J. H. Vaughan,Effect of iron dextran, gold thiosulphate and hydrocortisone acetate on experimental synovitis in the guinea-pig. Ann. Rheum. Dis.30, 187–193 (1971).

    PubMed  Google Scholar 

  18. P. G. Winyard, D. R. Blake, S. Chirico, J. M. C. Gutteridge and J. Lunec,Mechanism of exacerbation of rheumatoid synovitis by total-dose iron-dextran infusion: in-vivo demonstration of iron-promoted oxidant-stress. Lancet 69–72 (1987).

  19. V. M. Samokyszyn, D. M. Miller, D. W. Reif and S. D. Aust,Inhibition of superoxide and ferritin-dependent lipid peroxidation by ceruloplasmin. J. Biol. Chem.264, 21–26 (1989).

    PubMed  Google Scholar 

  20. I. M. Hoepelman, E. Y. Jaarsma, J. Verhoef and J. J. M. Marx,Effect of iron on polymorphonuclear granulocyte phagocytic capacity: role of oxidation state and effect of ascorbic acid. Br. J. Haematol.70, 495–500 (1988).

    PubMed  Google Scholar 

  21. G. Curzon and S. O'Reilly,A coupled iron-caeruloplasmin oxidation system. Biochem. Biophys. Res. Com.2, 284–286 (1960).

    Article  Google Scholar 

  22. E. Graf, J. R. Mahoney, R. G. Bryant and J. W. Eaton,Iron catalyzed hydroxyl radical formation. J. Biol. Chem.259, 3620–3624 (1984).

    PubMed  Google Scholar 

  23. J. Sinaceur, C. Ribière, J. Nordmann and R. Nordmann,Desferrioxamine: a scavenger of superoxide radicals? Biochem. Pharmacol.33, 1693–1694 (1984).

    Article  PubMed  Google Scholar 

  24. D. R. Blake, N. D. Hall, P. A. Bacon, P. A. Dieppe, B. Halliwell and J. M. C. Gutteridge,Effect of a specific iron chelating agent on animal models of inflammation. Ann. Rheum. Dis.42, 89–93 (1983).

    PubMed  Google Scholar 

  25. F. J. Andrews, C. J. Morris, G. Kondratowicz and D. R. Blake,Effect of iron chelation on inflammatory joint disease. Ann. Rheum. Dis.46, 327–333 (1987).

    PubMed  Google Scholar 

  26. S. Yoshino, D. R. Blake and P. A. Bacon,The effect of desferrioxamine on antigen-induced inflammation in the rat air pouch. J. Pharm. Pharmacol.36, 543–545 (1984).

    PubMed  Google Scholar 

  27. M. T. Mitjavila, M. T. Carbonell, M. P. Sáiz, J. Muntané, J. Sánchez and P. Puig-Parellada,Role of iron in carrageenan-induced granuloma: Action of desferrioxamine and indometacin. Pharmacol.40, 236–240 (1990).

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Unitat de Fisiologia, Facultat de Biologia, Universitat de Barcelona, 08028, Barcelona, Spain

    J. Muntane, T. Carbonell, M. P. Saiz & M. T. Mitjavila

  2. U-87 INSERM, Institut de Physiologie, 31400, Toulouse, France

    P. Fritsch

  3. Unitat de Farmacologia, Facultat de Medicina, Universitat de Barcelona, 08028, Barcelona, Spain

    P. Puig-Parellada

Authors
  1. J. Muntane
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P. Fritsch
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T. Carbonell
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. P. Saiz
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. P. Puig-Parellada
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M. T. Mitjavila
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Muntane, J., Fritsch, P., Carbonell, T. et al. Modulation of exudate inflammation parameters in rat carrageenan-induced granuloma by modification of exudate iron levels. Agents and Actions 32, 167–172 (1991). https://doi.org/10.1007/BF01980869

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01980869

Keywords

Search

Navigation