Abstract
Thein 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 cytochromec (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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Truelove SC, Watkinson G, Draper G: Comparison of corticosteroids and sulphasalazine therapy in ulcerative colitis. Br Med J 2:1708–1711, 1962
Dissanayake AS, Truelove SC: A controlled therapeutic trial of long-term maintenance treatment of ulcerative colitis with sulphasalazine (Salazopyrin). Gut 14:923–926, 1973
Peppercorn MA, Goldman P: Distribution studies of salicylazosulphapyridine and its metabolites. Gastroenterology 64:240–245, 1973
Azad Khan AK, Piris J, Truelove SC: An experiment to determine the active moiety of sulphasalazine. Lancet 2:892–895, 1977
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
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
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
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
Cominelli F, Zipser RD, Dinarello CA: Sulphasalazine inhibits cytokine production in human mononuclear cells: A novel anti-inflammatory mechanism. Gastroenterology 96:A96, 1989
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
Grisham MB, Granger DN: Neutrophil-mediated mucosal injury. Role of reactive oxygen metabolites. Dig Dis Sci 33:6s-15s, 1988
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
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
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
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
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
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
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
Stenson WF, Lobos E: Sulphasalazine inhibits the synthesis of chemotactic lipids by neutrophils. J Clin Invest 69:494–497, 1982
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
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
Yoshimoto G, Yoshimoto T, Tsubura E: Arachidonic acid-induced chemiluminescence of human polymorphonuclear leukocytes. Biochem Biophys Res Commun 107:779–784, 1982
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
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
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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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DOI: https://doi.org/10.1007/BF01300752