Scavenger effect of sulfasalazine, 5-aminosalicylic acid, and olsalazine on superoxide radical generation (original) (raw)

Abstract

The_in vitro_ antioxidant capacity of sulfasalazine (SASP), its metabolites (SP, 5-SSA), and olsalazine (OAZ), was studied by evaluating their effects on superoxide (O2 − •) production. Assay systems were the xanthine-xanthine oxidase (X/XOD) reaction and phorbol myristate acetate (PMA)-activated polymorphonuclear leukocytes (PMNs), using the cytochrome_c_ (cyt-c) reduction assay and a luminol-dependent chemiluminescence method. 5-ASA, SASP, and OAZ showed a dose-dependent scavenger effect in both O2 − • generating systems, 5-ASA being the most powerful (>50% of inhibition in the PMNs system and >70% in the X/XOD system at 10 μM concentration). SP had an inhibitory effect only in the PMNs system but did not modify the activity of xanthine oxidase, thus excluding a scavenger action. These data suggest that the scavenger effect of 5-ASA, SASP, and OAZ may be an important mechanism of action.

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References

1. Truelove SC, Watkinson G, Draper G: Comparison of corticosteroids and sulphasalazine therapy in ulcerative colitis. Br Med J 2:1708–1711, 1962
   Google Scholar
2. Dissanayake AS, Truelove SC: A controlled therapeutic trial of long-term maintenance treatment of ulcerative colitis with sulphasalazine (Salazopyrin). Gut 14:923–926, 1973
   Google Scholar
3. Peppercorn MA, Goldman P: Distribution studies of salicylazosulphapyridine and its metabolites. Gastroenterology 64:240–245, 1973
   Google Scholar
4. Azad Khan AK, Piris J, Truelove SC: An experiment to determine the active moiety of sulphasalazine. Lancet 2:892–895, 1977
   Google Scholar
5. Van Hees PAM, Bakker JH, Van Tongeren JHM: Effect of sulphapyridine, 5-aminosalicylic acid and placebo in patients with ulcerative colitis and Crohn's disease. Gut 21:632–635, 1980
   Google Scholar
6. Klotz U, Maier K, Fischer C, Heinkel K: Therapeutic efficacy of sulphasalazine and its metabolites in patients with ulcerative colitis and Crohn's disease. N Engl J Med 303:1499–1502, 1980
   Google Scholar
7. Nielsen OH, Bukhave K, Elmgreen J, Ahnfelt-Ronne I: Inhibition of 5-lipoxygenase pathway of arachidonic acid metabolism in human neutrophils by sulfasalazine and 5-aminosalicylic acid. Dig Dis Sci 32:577–582, 1987
   Google Scholar
8. Eliakim R, Karmeli F, Razin E, Rachmilewitz D: Role of platelet activating factor in ulcerative colitis: Inhibition by sulphasalazine and prednisolone. Gastroenterology 95:1167–1173, 1988
   Google Scholar
9. Cominelli F, Zipser RD, Dinarello CA: Sulphasalazine inhibits cytokine production in human mononuclear cells: A novel anti-inflammatory mechanism. Gastroenterology 96:A96, 1989
   Google Scholar
10. Lamming CED, Mahida YR, Hawkey CJ: 5-aminosalicylic acid (5-ASA) inhibits interleukin 1B (IL 1B) production by colonic biopsies in organ culture. Gastroenterology 96:A285, 1989
    Google Scholar
11. Grisham MB, Granger DN: Neutrophil-mediated mucosal injury. Role of reactive oxygen metabolites. Dig Dis Sci 33:6s-15s, 1988
    Google Scholar
12. Dull BJ, Salata K, Van Langenhove A, Goldman P: 5-Aminosalicylate: Oxidation by activated leukocytes and protection of cultured cells from oxidative damage. Biochem Pharmacol 36:2467–2472, 1987
    Google Scholar
13. Craven PA, Pfanstiel J, Saito R, De Rubertis FR: Actions of sulphasalazine and 5-aminosalicylic acid as reactive oxygen scavengers in the suppression of bile acid-induced increases in colonic epithelial cell loss and proliferative activity. Gastroenterology 92:1998–2008, 1987
    Google Scholar
14. Miyachi Y, Yoshioka A, Imamura S, Niwa Y: Effect of sulphasalazine and its metabolites on the generation of reactive oxygen species. Gut 28:192–195, 1987
    Google Scholar
15. Molin L, Stendhal O. The effect of sulphasalazine and its active component on human polymorphonuclear leucocyte function in relation to ulcerative colitis. Acta Med Scand 206:451–457, 1979
    Google Scholar
16. Neal TM, Winterbourn CC, Vissers MC: Inhibition of neutrophil degranulation and superoxide production by sulphasalazine. Comparison with 5-aminosalicylic acid, sulphapyridine and olsalazine. Biochem Pharmacol 36:2765–2768, 1987
    Google Scholar
17. Nielsen OH:In vitro studies on the significance of arachidonate metabolism and other oxidative processes in the inflammatory response of human neutrophils and macrophages. With special reference to chronic inflammatory bowel disease. Scand J Gastroenterol 23(suppl 150):3–21, 1988
    Google Scholar
18. Williams JG, Hallett MB: Effect of sulphasalazine and its active metabolite, 5-aminosalicylic acid, on toxic oxygen metabolite production by neutrophils. Gut 30:1581–1587, 1989
    Google Scholar
19. Stenson WF, Lobos E: Sulphasalazine inhibits the synthesis of chemotactic lipids by neutrophils. J Clin Invest 69:494–497, 1982
    Google Scholar
20. Summers RW, Switz DM, Sessions JT, Becktel JM, Best WR, Kern JR, Singleton JW: National cooperative Crohn's disease study: Results of drug treatment. Gastroenterology 77:847–869, 1979
    Google Scholar
21. Sharon P, Stenson WF: Metabolism of arachidonic acid in acetic acid colitis in rats. Similarity to human inflammatory bowel disease. Gastroentorology 88:55–63, 1985
    Google Scholar
22. Yoshimoto G, Yoshimoto T, Tsubura E: Arachidonic acid-induced chemiluminescence of human polymorphonuclear leukocytes. Biochem Biophys Res Commun 107:779–784, 1982
    Google Scholar
23. Baud L, Nivez MP, Chansel D, Ardaillou R: Stimulation by oxygen radicals of prostaglandin production by rat renal glomeruli. Kidney Int 20:332–339, 1981
    Google Scholar
24. Ahnfelt-Ronne I, Haagen Nielsen O, Christensen A, Langholz E, Binder V, Riis P: Clinical evidence supporting the radical scavenger mechanism of 5-aminosalicylic acid. Gastroenterology 98:1162–1169, 1990
    Google Scholar

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Authors and Affiliations

1. Istituto di Clinica Medica e Gastroenterologia, Dipartimento di Biochimica, Università di Bologna, Policlinico S. Orsola, Via Massarenti 9, 40138, Bologna, Italy
   P. Gionchetti MD, C. Guarnieri MD, M. Campieri MD, A. Belluzzi MD, C. Brignola MD, P. Iannone MD, M. Miglioli MD & L. Barbara MD

Authors

1. P. Gionchetti MD
2. C. Guarnieri MD
3. M. Campieri MD
4. A. Belluzzi MD
5. C. Brignola MD
6. P. Iannone MD
7. M. Miglioli MD
8. L. Barbara MD

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Gionchetti, P., Guarnieri, C., Campieri, M. et al. Scavenger effect of sulfasalazine, 5-aminosalicylic acid, and olsalazine on superoxide radical generation.Digest Dis Sci 36, 174–178 (1991). https://doi.org/10.1007/BF01300752

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• Received: 01 March 1990
• Revised: 10 July 1990
• Accepted: 13 August 1990
• Issue date: February 1991
• DOI: https://doi.org/10.1007/BF01300752

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