Agents and Actions

, Volume 16, Issue 5, pp 377–384 | Cite as

Effect of anti-inflammatory drugs on xanthine oxidase and xanthine oxidase induced depolymerization of hyaluronic acid

  • G. Carlin
  • R. Djursäter
  • G. Smedegård
  • B. Gerdin
Immunosuppression and Inflammation


The inhibitory effect of various anti-inflammatory drugs on the xanthine oxidase derived depolymerization of hyaluronic acid was studied. The depolymerization was assayed by repeated viscosity measurements. By using a low xanthine oxidase activity, the decrease in viscosity with time followed first order reaction kinetics and was therefore suitable for kinetic analysis. The xanthine oxidase activity was monitored by assay of O2-consumption with a Clark-electrode and by assay of ureate production.

We present evidence that salicylic, acetylsalicylic, gentisic and azodisalicylic acid and sulfasalazine inhibit the production of oxygen-derived free radicals by xanthine oxidase. We found that sulfapyridine, 5-aminosalicylic acid, allopurinol, mannitol, glucuronic acid andN-acetylglucoseamine in addition to the earlier studied drugs, paracetamol, ibuprofen, benoxaprofen and gentisic acid exert their effect via seavenging of free radicals. These drugs had very little effect on the enzyme activity.


Mannitol Ibuprofen Paracetamol Hyaluronic Acid Xanthine Oxidase 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. [1]
    E.A. Balasz, The physical properties of synovial fluid and the special role of hyaluronic acid. InDisorders of the Knee (Ed.A. Helfet). J.B. Lippincot, Philadelphia 1974.Google Scholar
  2. [2]
    J.M. McCord,Free radicals and inflammation: protection of synovial fluid by superoxide dismutase, Science185, 529–531 (1974).PubMedGoogle Scholar
  3. [3]
    R.A. Greenwald andW.W. Moy,Effect of oxygen-derived free radicals on hyaluronic acid, Arthritis Rheum.23, 455–463 (1980).PubMedGoogle Scholar
  4. [4]
    B. Halliwell,Superoxide-dependent formation of hydroxyl radicals in the presence of iron salts, FEBS Lett.96, 238–242 (1978).CrossRefGoogle Scholar
  5. [5]
    P. Puig-Parellada andJ.M. Planas,Synovial fluid degradation induced by free radicals: in vitro action of several free radical scavengers and anti-inflammatory drugs, Biochem. Pharmac.27, 535–537 (1978).CrossRefGoogle Scholar
  6. [6]
    R.F. Del Maestro,Influence of oxygen derived free radicals on in vivo model systems, Acta Universitatis Upsaliensis, Abstracts of Uppsala dissertation from the faculty of medicine 340 (1979).Google Scholar
  7. [7]
    R.F. Del Maestro, H.H. Thaw, J. Björk, K. Planker andK.-E. Arfors,Free radicals as mediators of tissue injury, Acta physiol. Scand.492, 43–57 (1980).Google Scholar
  8. [8]
    W.H. Betts andL.G. Cleland,Effect of metal chelators and anti-inflammatory drugs on degradation of hyaluronic acid. Arthritis Rheum.25, 1469–1476 (1982).PubMedGoogle Scholar
  9. [9]
    L.G. Cleland, W.H. Betts, B. Vernon-Roberts andJ. Bielicki,Role of iron and influence of anti-inflammatory drugs on oxygenderived radical production and reactivity, J. Rheumatol.9, 885–892 (1982).PubMedGoogle Scholar
  10. [10]
    W.R. Waud, F.O. Brady, R.D. Wiley andK.V. Rajagopalan,A new purification procedure for bovine milk xanthine oxidase, Archs Biochem. Biophys.169, 695–701 (1975).CrossRefGoogle Scholar
  11. [11]
    G. Carlin, J.W. Ryan andT. Saldeen,Assays of components of the kallikrein-kinin system based on first order reaction kinetics, Adv. exp. Med. Biol.156B, 797–804 (1983).Google Scholar
  12. [12]
    G.B. Elion,Enzymatic and metabolic studies with allopurinol, Ann. rheum. Dis.25, 608–614 (1966).PubMedGoogle Scholar
  13. [13]
    J.A. Kofoed andA.C. Barceló,The synovial fluid hyaluronic acid in rheumatoic arthritis, Experientia34, 1545–1546 (1978).PubMedGoogle Scholar
  14. [14]
    B. Halliwell,Superoxide-dependent formation of hydroxyl radicals in the presence of iron chelates, FEBS Lett.92, 321–326 (1978b).CrossRefGoogle Scholar
  15. [15]
    B. Halliwell andJ.M.C. Gutteridge,Oxygen toxicity, oxygen radicals, transition metals and disease, Biochem. J.219, 1–14 (1984).PubMedGoogle Scholar
  16. [16]
    S.A. Metz,Anti-inflammatory agents as inhibitors of Prostaglandin synthesis in man. Med. Clins N. Am.65, 713–757 (1981).Google Scholar
  17. [17]
    W.H. Betts, M.W. Whitehouse andL.G. Cleland,Potentiation of the antioxidant capacity of salicylate by oxygen radicals. XXIX congress of international union of physiological sciences, Sydney, Australia 28 August—3 September 1983, abstract 262–05 (1983).Google Scholar
  18. [18]
    R.J. Flower andJ.R. Vane, Some pharmacologic and biochemical aspects of prostaglandin biosynthesis and its inhibition. InProstaglandin Synthetase Inhibitors. Raven Press,N.Y. 1974.Google Scholar
  19. [19]
    M.D. Rawlins, D.B. Henderson andA.R. Hijab,Pharmacokinetics of paracetamol (acetaminophen) after intravenous and oral administration, Eur. J.Clin. Pharmac.11, 283–286 (1977).CrossRefGoogle Scholar
  20. [20]
    G.F. Lockwood, K.S. Albert, W.R. Gillespie, G.G. Bole, T.M. Harkom, G.J. Szpunar andJ.G. Wagner,Pharmacokinetics of ibuprofen in man. Free and total area/dose relationships, Clin. Pharmac. Ther.34, 97–103 (1983).Google Scholar
  21. [21]
    J.M. Brogard, F. Comte, M. Madon andM.O. Spach,Pharmacokinetic profile of benoxaprofen in subjects with normal and impaired renal function. Prediction of multiple-dose kinetics, Eur. J. Rheumatol. Inflamm.5, 113–123 (1982).PubMedGoogle Scholar
  22. [22]
    D.E.S. Campbell,Therapie der Colitis ulcerosa mit Sulfasalazine-heute und morgen, Verdauungskrankheiten1, 40–46 (1983).Google Scholar
  23. [23]
    J.R.S. Hoult &P.K. Moore, Prostaglandin and the mode of action of sulphasalazine in ulcerative colitis: two opposing viewpoints. InInflammatory Bowel Diseases (Ed.D. Rachmilewitz). Nijhoff, London 1982.Google Scholar
  24. [24]
    R.W. Egan, J. Paxton andF.A. Kuehl Jr.,Mechanism for irreversible self-deactivation of prostaglandin synthetase, J. biol. Chem.251, 7329–7335 (1976).PubMedGoogle Scholar
  25. [25]
    K. Lauritsen, J. Hansen, M. Ryde andJ. Rask-Madsen,Colonic azodisalicylate metabolism determined by in vivo dialysis in healthy volunteers and patients with ulcerative colitis, Gastroenterology86, 1496–1500 (1984).PubMedGoogle Scholar

Copyright information

© Birkhäuser Verlag 1985

Authors and Affiliations

  • G. Carlin
    • 1
  • R. Djursäter
    • 1
  • G. Smedegård
    • 1
  • B. Gerdin
    • 1
  1. 1.Department of Experimental Medicine, Pharmacia AB and Department of SurgeryUniversity HospitalUppsalaSweden

Personalised recommendations