Abstract
The mucosal protective prostaglandin analogs misoprostol, enisoprost, and SC-46275 (the 17E-18-cyclopentenyl analog of enisoprost) were tested in mouse and rat colitis induced by the intrarectal instillation of dilute acetic acid. Colitis was assessed by histology and colonic levels of myeloperoxidase (a neutrophil marker enzyme). When given as enemas 30 min ahead of colitis induction, 15(R)-15-methyl-PGE2 (arbaprostil) and 15(S)-15-methyl-PGE1 were inactive; however, misoprostol, enisoprost, and SC-46275 protected against colonic inflammation with ED50 values of 24, 12 and 1.3μg/kg, respectively, in rats and 11, 5, and 1μg/kg, respectively, in mice. These compounds may have utility in the medical management of human inflammatory bowel disease.
Similar content being viewed by others
References
MacDermott, R. P., andW. F. Stenson. 1988. Alterations of the immune system in ulcerative colitis and Crohn's disease.Adv. Immunol. 42:285–328.
Sharon, P., andW. F. Stenson. 1984. Enhanced synthesis of leukotriene B4 by colonie mucosa in inflammatory bowel disease.Gastroenterology 86:453–460.
Stenson, W. F. 1988. Arachidonic acid metabolites in inflammatory bowel disease.Adv. Inflam. Res. 12:215–222.
Norris, A. A., 1989. Animal models of inflammatory bowel disease.In Pharmacological Methods in the Control of Inflammation. J. Y. Chang, A. J. Lewis, editors. Alan R. Liss, New York. 321–342.
Fretland, D. J., S. Levin, B. S. Tsai, S. W. Djuric, D. L. Widomski, J. M. Zemaitis, R. L. Shone, andR. F. Bauer. 1989. The effect of the leurotriene B4 receptor antagonist, SC-41930, on acetic acid induced colonic inflammation.Agents Actions 27:395–397.
Allgayer, H., K. Deschryver, andW. F. Stenson. 1989. Treatment with 16,16-dimethyl-prostaglandin E2 before and after induction of colitis with trinitrobenzenusulfonic acid in rats decreases inflammation.Gastroenterology 96:1290–1300.
Schumert, R., C. C. Nast, F. Cominelli, andR. D. Zipser. 1988. Effects of 16,16-dimethyl prostaglandin E2 and indomethacin on leukotriene B4 and inflammation in rabbit colitis.Prostaglandins 36:565–577.
Fedorak, R. N., L. R. Empey, C. MacArthur, andL. D. Jewell. 1990. Misoprostol provides a colonic mucosal protective effect during acetic acid-induced colitis in rats.Gastroenterology 98:615–625.
Collins, P. W. 1990. Misoprostol: Discovery, development and clinical applications.Med. Res. Rev. 10:149–172.
Collins, P. W., A. F. Gasiecki, W. E. Perkins, G. W. Gullikson, R. G. Bianchi, S. W. Kramer, J. S. Ng, E. E. Yonan, L. Swenton, P. H. Jones, andR. F. Bauer. 1990. Chemistry and structure-activity relationships of C-17 unsaturated 18-cycloalkyl and cycloalkenyl analogues of enisoprost.J. Med. Chem. 33:2784–2793.
Krawisz, J., P. Sharon, andW. F. Stenson. 1984. Quantitative assay for acute intestinal inflammation based on myeloperoxidase activity.Gastroenterology 87:1344–1350.
Keith, R., W. Smith, B. Tsai, S. Levin, andG. Butchko. 1985. Myeloperoxidase activity in experimentally induced colitis.Fed. Proc. 44:1545.
Boughton-Smith, N. K., J. L. Wallace, andB. J. R. Whittle. 1988. Relationships between arachidonic acid metabolism, myeloperoxidase activity and leukocyte infiltration in a rat model of inflammatory bowel disease.Agents Actions 25:115–123.
Rachmilewitz, D., P. Simon, L. Schwartz, D. Griswold, J. Fondacaro, andM. Wasserman. 1989. Inflammatory mediators of experimental colitis in rats.Gastroenterology 97:326–337.
Miller, M. J. S., X. -J, Zhang, X. Gu, andD. A. Clark. 1991. Acute intestinal injury induced by acetic acid and casein: Prevention by intraluminal misoprostol.Gastroenterology 101:22–30.
Goldin, E., andD. Rachmilewitz. 1983. Prostanoids cytoprotection for maintaining remission in ulcerative colitis: Failure of 15(R)-15-methyl prostaglandin E2.Dig. Dis. Sci. 28:807–811.
Collins, P. W. 1986. Development and therapeutic role of synthetic prostaglandins in peptic ulcer disease.J. Med. Chem. 29:437–443.
Torsher, K. J., L. K. Empey, andR. N. Fedorak. 1992. Misoprostol therapy following trinitrobenzene sulfonic acid-induced colitis accelerates healing.Prostaglandins Leukotrienes Essent. Fatty Acids 45:275–281.
Perkins, W. E., P. W. Collins, R. G. Bianchi, A. F. Gasiecki, R. F. Bauer, P. H. Jones, andT. S. Gaginella. 1991. Antisecretory, mucosal-protective and diarrhreagenic activity of a novel synthetic prostaglandin, SC-46275, in the rat.Drug Dev. Res. 23:349–358.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Fretland, D.J., Widomski, D.L., Anglin, C.P. et al. Mucosal protective activity of prostaglandin analogs in rodent colonic inflammation. Inflammation 16, 623–629 (1992). https://doi.org/10.1007/BF00919345
Issue Date:
DOI: https://doi.org/10.1007/BF00919345