Skip to main content
Gut logoLink to Gut
. 1984 Nov;25(11):1271–1278. doi: 10.1136/gut.25.11.1271

Effects of sulphasalazine and disodium azodisalicylate on colonic PGE2 concentrations determined by equilibrium in vivo dialysis of faeces in patients with ulcerative colitis and healthy controls.

K Lauritsen, J Hansen, P Bytzer, K Bukhave, J Rask-Madsen
PMCID: PMC1432314  PMID: 6149981

Abstract

The role of arachidonic acid metabolites and the mode of action of 5-aminosalicylic acid, the active moiety of sulphasalazine and disodium azodisalicylate, in ulcerative colitis remain obscure. Therefore, experiments were performed in which the effects of medication on immunoreactive prostaglandin (PG) E2 concentrations in free faecal water were assessed using the equilibrium in vivo dialysis of faeces. Colonic PGE2 concentrations in patients with active ulcerative colitis (n = 11) ranged from 2035-18,000 pg/ml to be compared with a range of 103-188 pg/ml in healthy volunteers (n = 10; p less than 0.001). In all healthy volunteers PGE2 concentrations decreased slightly (p less than 0.05) after disodium azodisalicylate intake 2 g/day, whereas low dose disodium azodisalicylate (0.25 g/day) caused no change. In patients with ulcerative colitis in complete clinical, sigmoidoscopic, and histologic remission withdrawal of sulphasalazine (2 g/day; n = 6) increased PGE2 concentrations to values above normal levels (p less than 0.05) which returned to pretrial values (p less than 0.05) on disodium azodisalicylate (2 g/day; n = 7). In conclusion, increased PGE2 in free faecal water indicates an abnormality in the colonic mucosa, even in the absence of conventional signs of inflammation. We could not confirm the hypothesis that sulphasalazine and 5-aminosalicylic acid exert their therapeutic effect through promotion of endogenous cytoprotective prostaglandins. In contrast, the observation that raised PGE2 concentrations were normalised by disodium azodisalicylate in patients with inactive ulcerative colitis suggests that subclinical disease activity was decreased by 5-aminosalicylic acid.

Full text

PDF
1271

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Azad Khan A. K., Howes D. T., Piris J., Truelove S. C. Optimum dose of sulphasalazine for maintenance treatment in ulcerative colitis. Gut. 1980 Mar;21(3):232–240. doi: 10.1136/gut.21.3.232. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Azad Khan A. K., Piris J., Truelove S. C. An experiment to determine the active therapeutic moiety of sulphasalazine. Lancet. 1977 Oct 29;2(8044):892–895. doi: 10.1016/s0140-6736(77)90831-5. [DOI] [PubMed] [Google Scholar]
  3. BARON J. H., CONNELL A. M., LENNARD-JONES J. E. VARIATION BETWEEN OBSERVERS IN DESCRIBING MUCOSAL APPEARANCES IN PROCTOCOLITIS. Br Med J. 1964 Jan 11;1(5375):89–92. doi: 10.1136/bmj.1.5375.89. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Boughton-Smith N. K., Hawkey C. J., Whittle B. J. Biosynthesis of lipoxygenase and cyclo-oxygenase products from [14C]-arachidonic acid by human colonic mucosa. Gut. 1983 Dec;24(12):1176–1182. doi: 10.1136/gut.24.12.1176. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bukhave K., Gréen K., Rask-Madsen J. Comparison of radioimmunological determinations with gas chromatography mass spectrometry dosage. A study of PGE2 and PGF2alpha in gastrointestinal fluids. Biomed Mass Spectrom. 1983 Apr;10(4):265–268. doi: 10.1002/bms.1200100406. [DOI] [PubMed] [Google Scholar]
  6. Bukhave K., Rask-Madsen J. Prostaglandin E2 in jejunal fluids and its potential diagnostic value for selecting patients with indomethacin-sensitive diarrhoea. Eur J Clin Invest. 1981 Jun;11(3):191–197. doi: 10.1111/j.1365-2362.1981.tb01840.x. [DOI] [PubMed] [Google Scholar]
  7. Campieri M., Lanfranchi G. A., Bazzocchi G., Brignola C., Benatti A., Boccia S., Labo' G. Prostaglandins, indomethacin, and ulcerative colitis. Gastroenterology. 1980 Jan;78(1):193–193. [PubMed] [Google Scholar]
  8. Campieri M., Lanfranchi G. A., Bazzocehi G., Brignola C., Corazza G., Cortini C., Michelini M., Labó G. Salicylate other than 5-aminosalicylic acid ineffective in ulcerative colitis. Lancet. 1978 Nov 4;2(8097):993–993. doi: 10.1016/s0140-6736(78)92556-4. [DOI] [PubMed] [Google Scholar]
  9. Collier H. O., Francis A. A., McDonald-Gibson W. J., Saeed S. A. Inhibition of prostaglandin biosynthesis by sulphasalazine and its metabolites. Prostaglandins. 1976 Feb;11(2):219–225. doi: 10.1016/0090-6980(76)90145-3. [DOI] [PubMed] [Google Scholar]
  10. Gilat T., Ratan J., Rosen P., Peled Y. Prostaglandins and ulcerative colitis. Gastroenterology. 1979 May;76(5 Pt 1):1083–1083. [PubMed] [Google Scholar]
  11. Goldman P., Peppercorn M. A. Drug therapy: Sulfasalazine. N Engl J Med. 1975 Jul 3;293(1):20–23. doi: 10.1056/NEJM197507032930105. [DOI] [PubMed] [Google Scholar]
  12. Goldman P. Will there be a next generation of sulfasalazine? Gastroenterology. 1982 Nov;83(5):1138–1141. [PubMed] [Google Scholar]
  13. Gould S. R., Brash A. R., Conolly M. E., Lennard-Jones J. E. Studies of prostaglandins and sulphasalazine in ulcerative colitis. Prostaglandins Med. 1981 Feb;6(2):165–182. doi: 10.1016/0161-4630(81)90088-4. [DOI] [PubMed] [Google Scholar]
  14. Gould S. R. Letter: Prostaglandins, ulcerative colitis, and sulphasalazine. Lancet. 1975 Nov 15;2(7942):988–988. doi: 10.1016/s0140-6736(75)90414-6. [DOI] [PubMed] [Google Scholar]
  15. Harris D. W., Smith P. R., Swan C. H. Determination of prostaglandin synthetase activity in rectal biopsy material and its significance in colonic disease. Gut. 1978 Oct;19(10):875–877. doi: 10.1136/gut.19.10.875. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hawkey C. J., Lo Casto M. Inhibition of prostaglandin synthetase in human rectal mucosa. Gut. 1983 Mar;24(3):213–217. doi: 10.1136/gut.24.3.213. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hoult J. R., Moore P. K. Effects of sulphasalazine and its metabolites on prostaglandin synthesis, inactivation and actions on smooth muscle. Br J Pharmacol. 1980 Apr;68(4):719–730. doi: 10.1111/j.1476-5381.1980.tb10865.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hoult J. R., Page H. 5-Aminosalicylic acid, a co-factor for colonic prostacyclin synthesis? Lancet. 1981 Aug 1;2(8240):255–255. doi: 10.1016/s0140-6736(81)90502-x. [DOI] [PubMed] [Google Scholar]
  19. Klotz U., Maier K., Fischer C., Heinkel K. Therapeutic efficacy of sulfasalazine and its metabolites in patients with ulcerative colitis and Crohn's disease. N Engl J Med. 1980 Dec 25;303(26):1499–1502. doi: 10.1056/NEJM198012253032602. [DOI] [PubMed] [Google Scholar]
  20. Lauritsen K., Hansen J., Ryde M., Rask-Madsen J. Colonic azodisalicylate metabolism determined by in vivo dialysis in healthy volunteers and patients with ulcerative colitis. Gastroenterology. 1984 Jun;86(6):1496–1500. [PubMed] [Google Scholar]
  21. Ligumsky M., Karmeli F., Sharon P., Zor U., Cohen F., Rachmilewitz D. Enhanced thromboxane A2 and prostacyclin production by cultured rectal mucosa in ulcerative colitis and its inhibition by steroids and sulfasalazine. Gastroenterology. 1981 Sep;81(3):444–449. [PubMed] [Google Scholar]
  22. Musch M. W., Miller R. J., Field M., Siegel M. I. Stimulation of colonic secretion by lipoxygenase metabolites of arachidonic acid. Science. 1982 Sep 24;217(4566):1255–1256. doi: 10.1126/science.6810465. [DOI] [PubMed] [Google Scholar]
  23. Rampton D. S., McNeil N. I., Sarner M. Analgesic ingestion and other factors preceding relapse in ulcerative colitis. Gut. 1983 Mar;24(3):187–189. doi: 10.1136/gut.24.3.187. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Rampton D. S., Sladen G. E. Prostaglandin synthesis inhibitors in ulcerative colitis: flurbiprofen compared with conventional treatment. Prostaglandins. 1981 Mar;21(3):417–425. doi: 10.1016/0090-6980(81)90087-3. [DOI] [PubMed] [Google Scholar]
  25. Rampton D. S., Sladen G. E. Relapse of ulcerative proctocolitis during treatment with non-steroidal anti-inflammatory drugs. Postgrad Med J. 1981 May;57(667):297–299. doi: 10.1136/pgmj.57.667.297. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Rampton D. S., Sladen G. E. The effect of sulphasalazine withdrawal on rectal mucosal function and prostaglandin E2 release in inactive ulcerative colitis. Scand J Gastroenterol. 1981;16(1):157–159. [PubMed] [Google Scholar]
  27. Rampton D. S., Sladen G. E., Youlten L. J. Rectal mucosal prostaglandin E2 release and its relation to disease activity, electrical potential difference, and treatment in ulcerative colitis. Gut. 1980 Jul;21(7):591–596. doi: 10.1136/gut.21.7.591. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Riis P. A critical survey of controlled studies in the treatment of ulcerative colitis and Crohn's disease. Clin Gastroenterol. 1980 May;9(2):351–369. [PubMed] [Google Scholar]
  29. Schwartz A. G., Targan S. R., Saxon A., Weinstein W. M. Sulfasalazine-induced exacerbation of ulcerative colitis. N Engl J Med. 1982 Feb 18;306(7):409–412. doi: 10.1056/NEJM198202183060708. [DOI] [PubMed] [Google Scholar]
  30. Sharon P., Ligumsky M., Rachmilewitz D., Zor U. Role of prostaglandins in ulcerative colitis. Enhanced production during active disease and inhibition by sulfasalazine. Gastroenterology. 1978 Oct;75(4):638–640. [PubMed] [Google Scholar]
  31. Sircar J. C., Schwender C. F., Carethers M. E. Inhibition of soybean lipoxygenase by sulfasalazine and 5-aminosalicylic acid: a possible mode of action in ulcerative colitis. Biochem Pharmacol. 1983 Jan 1;32(1):170–172. doi: 10.1016/0006-2952(83)90673-1. [DOI] [PubMed] [Google Scholar]
  32. Stenson W. F., Lobos E. Sulfasalazine inhibits the synthesis of chemotactic lipids by neutrophils. J Clin Invest. 1982 Feb;69(2):494–497. doi: 10.1172/JCI110474. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. TRUELOVE S. C., WITTS L. J. Cortisone in ulcerative colitis; final report on a therapeutic trial. Br Med J. 1955 Oct 29;2(4947):1041–1048. doi: 10.1136/bmj.2.4947.1041. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. WRONG O., METCALFE-GIBSON A., MORRISON R. B., NG S. T., HOWARD A. V. IN VIVO DIALYSIS OF FAECES AS A METHOD OF STOOL ANALYSIS. I. TECHNIQUE AND RESULTS IN NORMAL SUBJECTS. Clin Sci. 1965 Apr;28:357–375. [PubMed] [Google Scholar]
  35. Willoughby C. P., Aronson J. K., Agback H., Bodin N. O., Truelove S. C. Distribution and metabolism in healthy volunteers of disodium azodisalicylate, a potential therapeutic agent for ulcerative colitis. Gut. 1982 Dec;23(12):1081–1087. doi: 10.1136/gut.23.12.1081. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. van Hees P. A., Bakker J. H., van Tongeren J. H. Effect of sulphapyridine, 5-aminosalicylic acid, and placebo in patients with idiopathic proctitis: a study to determine the active therapeutic moiety of sulphasalazine. Gut. 1980 Jul;21(7):632–635. doi: 10.1136/gut.21.7.632. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Gut are provided here courtesy of BMJ Publishing Group

RESOURCES