Skip to main content
Log in

Elevated levels of xanthine oxidase in serum of patients with inflammatory and autoimmune rheumatic diseases

  • Original Articles
  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

Sera of patients with various inflammatory and autoimmune rheumatic diseases were screened for the presence of xanthine oxidase (XOD) and compared to sera from healthy donors and patients with nonrheumatic diseases including AIDS, internal diseases, and different carcinomas. Up to 50-fold higher levels of XOD were detected in rheumatic sera (P < 0.001). In addition, serum sulfhydryls (SH) were determined as sensitive markers of oxidative stress. The SH status in rheumatic patients was diminished by 45–75% (P < 0.001) and inversely correlated to the concentration of serum XOD (R=0.73), suggesting a causal interrelation. The depletion of serum sulfhydryls by the oxyradical-producing XOD/acetaldehyde system was mimicked successfully ex vivo in human serum from healthy donors. Cortisone treatment of patients suffering from systemic lupus erythematosus and rheumatoid arthritis impressively normalized elevated XOD concentrations in rheumatic sera to those of healthy controls. The participation of xanthine oxidase in the depletion of serum antioxidants in rheumatic patients is discussed in the light of substrate availability andK m values.

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

Access this article

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. Stocker, R., andB. Frei. 1991. Endogenous antioxidant defences in human plasma.In Oxidative Stress. Oxidants and Antioxidants. H. Sies editor. Academic Press, London. 213–245.

    Google Scholar 

  2. Halliwell, B. 1991. Drug antioxidant effects. A basis for drug selection?Drugs 42:569–605.

    Google Scholar 

  3. Butler, J., B. M. Hoey, andJ. S. Lea. 1988.In Free Radicals, Methodology and Concepts. C. Rice-Evans and B. Halliwell, editors. Richelieu Press, London. 457–479.

    Google Scholar 

  4. Rice-Evans, C. A., A. T. Diplock, andM. C. R. Symons. 1991.In Techniques in Free Radical Research. R. H. Burdon, P. H. van Knippenberg, editors. Elsevier, Amsterdam. 1–291.

    Google Scholar 

  5. Staal, F. J. T., M. Roederer, andL. A. Herzenberg. 1990. Intracellular thiols regulate activation of nuclear factor kappa B and transcription of human immunedeficiency virus.Proc. Natl Acad. Sci. U.S.A. 87:9943–9947.

    Google Scholar 

  6. Engerson, T. D., T. G. McKelvey, D. B. Rhyne, E. B. Boggio, S. J. Snyder, andH. P. Jones. 1987. The conversion of xanthine dehydrogenase to oxidase in ischaemic rat tissueJ. Clin. Invest. 79:1564–1570.

    Google Scholar 

  7. Parks, D. A., andD. N. Granger. 1986. Xanthine oxidase: Biochemistry, distribution and physiology.Acta Physiol. Scand. 126(suppl. 548):87–99.

    Google Scholar 

  8. McCord, J. M. 1985. Oxygen-derived free radicals in post-ischaemic tissue injury.N. Engl. J. Med. 312:159–163.

    Google Scholar 

  9. McCord, J. M. 1985.In Superoxide Dismutase, Vol. III, Pathological States. L. Oberley, editor. CRC Press, Boca Raton. 143–150.

    Google Scholar 

  10. Grum, C. M., R. A. Ragsdale, L. H. Ketai, andR. H. Simon. 1987. Plasma hypoxanthine and exercise.Am. Rev. Respir. Dis. 136:98–101.

    Google Scholar 

  11. Petrone, W. F., D. K. English, K. Wong, andJ. M. McCord. 1980. Free radicals and inflammation: superoxide-dependent activation of a neutrophil chemotactic factor in plasma.Proc. Natl. Acad. Sci. U.S.A. 77:1159–1163.

    Google Scholar 

  12. Hartmann, H. J., A. Gaertner, andU. Weser. 1985. Copper dependent control of the enzymic and phagocyte induced degradation of some biopolymers, a possible link to systemic inflammation.Clin. Chim. Acta 152:95–103.

    Google Scholar 

  13. Woodruff, T., D. R. Blake, J. Freeman, F. J. Andrews, P. Salt, andJ. Lunec. 1986. Is chronic synovitis an example of reperfusion injury?Ann. Rheum. Dis. 45:608–611.

    Google Scholar 

  14. Blake, D. R., P. Merry, andJ. Unsworth. 1989. Hypoxic-reperfusion injury in the inflamed human joint.Lancet 1:289–293.

    Google Scholar 

  15. Linas, S. L., D. Whittenburg, andJ. E. Repine. 1990. Role of xanthine oxidase in ischemia/reperfusion injury.Am. J. Physiol. 258:711–716.

    Google Scholar 

  16. Puntarulo, S., andA. I. Cederbaum. 1989. Chemiluminescence from acetaldehyde oxidation by xanthine oxidase involves generation of and interactions with hydroxyl radicals.Alcohol Clin. Exp. Res. 13:84–90.

    Google Scholar 

  17. Grootveld, M., E. B. Henderson, A. Farrell, D. R. Blake, H. G. Parkes, andP. Haycock. 1991. Oxidative damage to hyaluronate and glucose in synovial fluid during exercise of the inflamed joint: detection of abnormal low molecular weight. Metabolites by proton nuclear magnetic resonance spectroscopy.Biochem. J. 273:459–467.

    Google Scholar 

  18. Nagano, T., andI. Fridovich. 1985. Does the aerobic xanthine oxidase reaction generate singlet oxygen?Photochem. Photobiol. 41:33–37.

    Google Scholar 

  19. Kelley, W. N., E. P. Harris Jr., andC. B. Sledge. 1989.In Textbook of Rheumatology. Saunders, Philadelphia.

    Google Scholar 

  20. Tan, E. M., A. S. Cohen, J. H. F. Fries, A. T. Masi, D. J. McShane, N. F. Rothfield, J. Schaller, N. Talal, andR. J. Winchester. 1982. The 1982 revised criteria for the classification of systemic lupus erythematosus.Arthritis Rheum. 25:1271–1277.

    Google Scholar 

  21. Redfield, R. R., D. C. Wright, andE. C. Tramont. 1986. The Walter Reed staging classification of HTLV-III/LAV infection.N. Engl. J. Med. 314:131–132.

    Google Scholar 

  22. Miesel, R., andU. Weser. 1991. Chemiluminescence assays of Cu2Zn2 superoxide dismutase mimicking Cu-complexes.Free Radic. Res. Commun. 12–13:253–258.

    Google Scholar 

  23. Allen, R. C. 1980. The Reticuloendothelial System.In The Reticuloendothelial System. Biochemistry and Metabolism, Vol. II. A. J. Sbarra and R. R. Strauss, editors. Plenum Press, New York. 309–338.

    Google Scholar 

  24. Metzler, D. E. 1977.In Biochemistry. The Chemical Reactions of Living Cells. D. E. Metzler editor. Oxidative Metabolism of Purines. Academic Press, New York. 881.

    Google Scholar 

  25. Miesel, R., H. J. Hartmann, Y. Li, andU. Weser. 1990. Reactivity of active centre analogues of Cu2Zn2 superoxide dismutase on polymorphonuclear leukocytes.Inflammation 14:409–419.

    Google Scholar 

  26. Miesel, R., andR. Haas. 1993. Reactivity of an active center analog of Cu2Zn2 superoxide dismustase in murine model of acute and chronic inflammation.Inflammation 17:595–611.

    Google Scholar 

  27. Badwey, J. A., J. M. Robinson, M. J. Karnovsky, andM. L. Karnovsky. 1986. Reduction and excitation of oxygen by phagocytic leucocytes: Biochemical and cytochemical techniques.In Handbook of Experimental Immunology. D. M. Weir, editor. Blackwell Scientific Publications, New York. 50.1–50.16.

    Google Scholar 

  28. Nakano, M. 1990. Determination of superoxide radical and singlet oxygen Chemiluminescence of luciferin analogues.Methods Enzymol. 186:585–591.

    Google Scholar 

  29. Yokoyama, Y., J. S. Beckman, andT. K. Beckman. 1990. Circulating xanthine oxidase: potential mediator of ischemic injury.Am. J. Physiol. 258:564–570.

    Google Scholar 

  30. Friedl, H. P., D. J. Smith, G. O. Till, P. D. Thomson, D. S. Louis, andP. A. Ward. 1990. Ischemia-reperfusion in humans. Appearance of xanthine oxidase activity.Am. J. Pathol. 136:491–495.

    Google Scholar 

  31. Redl, H., S. Hallstroem, C. Lieners, W. Fuerst, andG. Schlag. 1988.In Proteases II-Potential Role in Health and Disease. W. H. Hoerl and A. Heidland, editors. Plenum Press, New York. 449–455.

    Google Scholar 

  32. Friedl, H. P., G. O. Till, O. Trentz, andP. A. Ward. 1989. Role of histamine, complement and xanthine oxidase in thermal injury of skin.Am. J. Pathol. 135:203–217.

    Google Scholar 

  33. Lewis, M. S., R. E. Whatley, P. Cain, T. M. McIntyre, S. M. Prescott, andG. A. Zimmerman. 1988. Hydrogen peroxide stimulates the platelet-activating factor by endothelium and induces endothelial cell-dependent neutrophil adhesion.J. Clin. Invest. 82:2045–2055.

    Google Scholar 

  34. Hamer, D. H. 1986. Metallothionein.Annu. Rev. Biochem. 55:913–951.

    Google Scholar 

  35. Miesel, R., andM. Zuber. 1993. Copper-dependent antioxidase defenses in inflammatory and autoimmune rheumatic diseases.Inflammation 17:283–294.

    Google Scholar 

  36. Miesel, R. 1992. Potassiumperoxochromate arthritis in mice and rats.Biol. Chem. Hoppe-Seyler 373:879.

    Google Scholar 

  37. Miesel, R., H. J. Hartmann, andU. Weser. 1990. Antiinflammatory reactivity of copper(I)-thionein.Inflammation 14:471–483.

    Google Scholar 

  38. Thornalley, P. J., andM. Vasak. 1985. Possible role for metallothionein in protection against radiation induced oxidative stress. Kinetics and mechanisms of its reaction with superoxide and hydroxyl radicals.Biochem. Biophys. Acta 827:36–44.

    Google Scholar 

  39. Miesel, R., andU. Weser. 1989. Cu(I)-thionein and inflammation.Biol. Chem. Hoppe-Seyler 370:935–936.

    Google Scholar 

  40. Miesel, R., and M.Zuber. 1993. Reactive nitrogen intermediates, antinuclear antibodies and copper-thionein in serum of patients with rheumatic diseases.Rheumatol. Int. (in press).

  41. Blake, D. R. 1992. Free radicals as target for anti-inflammatory drugs.In An Update on Recent Advances in Inflammation Research. IBC, London.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Miesel, R., Zuber, M. Elevated levels of xanthine oxidase in serum of patients with inflammatory and autoimmune rheumatic diseases. Inflammation 17, 551–561 (1993). https://doi.org/10.1007/BF00914193

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00914193

Keywords

Navigation