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The antiinflammatory moiety of sulfasalazine, 5-aminosalicylic acid, is a radical scavenger

  • Immunosuppression and Inflammation
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Abstract

Using a novel spectrophotometric assay to detect free radical scavengers, the effects of sulfasalazine, a compound frequently administered in the treatment of chronic inflammatory bowel disease, and its main metabolites, 5-aminosalicylic acid (5-ASA), sulfapyridine, and N-acetyl-5-ASA, were compared with biological antioxidants (nordihydroguaiaretic, acid (NDGA), α-tocopherol, and ascorbic acid) and antiinflammatory salicylates (acetylsalicylic acid and sodium salicylate). The results show that 5-ASA, but neither sulfasalazine and its other metabolites, nor the salicylates, shares with the biological antioxidants the property of being a potent scavenger of free radicals. Since 5-ASA is formed in millimolar concentrations in the colon of sulfasalazine-treated patients this mode of action may explain the beneficial effect of sulfasalazine in inflammatory bowel disease. Locally formed 5-ASA may break the free radical chain reaction initiated and maintained by activated phagocytes, thus arresting the perpetuating tissue destruction. This mechanism may indicate a general potential for radical scavengers in chronic inflammation.

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References

  1. I. Fridovich,The biology of oxygen radicals. Science201, 875–880 (1978).

    Google Scholar 

  2. J. M. McCord,Free radicals and inflammation: Protection of synovial fluid by superoxide dismutase. Science185, 529–531 (1974).

    Google Scholar 

  3. D. Harman,Free radical theory of aging: Nutritional implications. Age1, 143–150 (1978).

    Google Scholar 

  4. G. Scott,Antioxidants in vitro and in vivo. Chem. Britain21, 648–653 (1985).

    Google Scholar 

  5. G. W. Burton and K. U. Ingold,β-Carotene: An unusual type of lipid antioxidant. Science224, 569–573 (1984).

    Google Scholar 

  6. J. M. McCord and I., Fridovich,Superoxide dismutase. An enzyme function for erythrocuprein (hemocuprein). J. Biol. Chem.224, 6049–6055 (1969).

    Google Scholar 

  7. S. Bondesen, O. H. Nielsen, J. B. Schou, P. H. Jensen, L. B. Lassen, V. Binder, P. A. Krasilnikoff, P. Danø, S. H. Hansen, S. N. Rasmussen and E. F. Hvidberg,Steady-state kinetics of 5-aminosalicylic acid and sulfapyridine during sulfasalazine prophylaxis in ulcerative colitis. Scand. J. Gastroenterol.21, 693–700 (1986).

    Google Scholar 

  8. M. A. Peppercorn,Sulfasalazine. Pharmacology, clinical use, toxicity, and related new drug development. Ann. Intern. Med.3, 377–386 (1984).

    Google Scholar 

  9. G. O. Schenck, M. Cziesla, K. Eppinger, G. Matthias and M. Pape,Isobenzpinakol als Ursache des Spektralen Effekts bei der Photoreduktion des Benzophenons. Tetrahedron Lett.3, 193–198 (1967).

    Google Scholar 

  10. O. H. Nielsen and S. Bondesen,Kinetics of 5-amino-salicylic acid after jenunal instillation in man. Br. J. Clin. Pharmacol.16, 738–740 (1983).

    Google Scholar 

  11. P. Sharon and W. F. Stenson,Enhanced synthesis of leukotrienes by colonic mucosa in inflammatory bowel disease. Gastroenterol.86, 453–460 (1984).

    Google Scholar 

  12. K. Lauritsen, J. Hansen, P. Bytzer, K. Bukhave and J. Rask-Madsen,Effects of sulfasalazine and disodium azadisalicylate on colonic PGE 2 levels determined by equilibrium in vivo dialysis of faeces in patients with ulcerative colitis and healthy controls. Gut.25, 1271–1278 (1984).

    Google Scholar 

  13. C. Deby, I. Pincemail, P. Hans, P. Braquet, Y. Lion, G. Deby-Dupont and R. Goutier,Mechanisms of free radicals production in the AA cascade, and role of anti-lipoperoxidants and free radical scavengers. In:Cerebral ischemia, pp. 249–258 (Eds. A. Bes, P. Braquet, R. Paoletti and B. K. Siesjö). Elsevier Science Publishers B. V., New York 1984.

    Google Scholar 

  14. I. Ahnfelt-Rønne and E. Arrigoni-Martelli,Effects of nonsteroidal antiinflammatory agents on arachidonic acid metabolism. Adv. Inflam. Res.8, 83–112 (1984).

    Google Scholar 

  15. W. Roediger, G. Schapel, M. Lawson, B. Radcliffe and S. Nance,Effects of 5-aminosalicylic acid (5-ASA) and other salicylates on short-chain fat metabolism in the colonic mucosa. Biochem. Pharmacol.35, 221–225 (1986).

    Google Scholar 

  16. G. Carlin, R. Djursäter, G. Smedegård and B. Gerdin,Effect of anti-inflammatory drugs on xanthine oxidase and xanthine oxidase induced depolymerisation of hyaluronic acid. Agents Actions16, 377–384 (1985).

    Google Scholar 

  17. V. W. Stuyvesant and W. B. Jolley,Anti-inflammatory activity of d -α-tocopherol (Vitamin E) and linoleic acid. Nature216, 585–586 (1967).

    Google Scholar 

  18. K. Grankvist, S. Marklund and I. B. Täljedal,Superoxide dismutase is a prophylactic against alloxan diabetes. Nature294, 158–160 (1981).

    Google Scholar 

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Authors and Affiliations

  1. Dept. of Pharmacology, Leo Pharmaceutical Products, DK-2750, Ballerup, Denmark

    I. Ahnfelt-Rønne

  2. Dept. of Medical Gastroenterology C, Herlev Hospital, University of Copenhagen, DK-2730, Herlev, Denmark

    O. Haagen Nielsen

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  1. I. Ahnfelt-Rønne
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  2. O. Haagen Nielsen
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Ahnfelt-Rønne, I., Haagen Nielsen, O. The antiinflammatory moiety of sulfasalazine, 5-aminosalicylic acid, is a radical scavenger. Agents and Actions 21, 191–194 (1987). https://doi.org/10.1007/BF01974941

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  • DOI: https://doi.org/10.1007/BF01974941

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