Role of Eicosanoids in the Pathogenesis of Inflammatory Bowel Diseases
The eicosanoids are metabolites of the essential fatty acid arachidonic acid formed via the cyclo-oxygenase and lipoxygenase enzyme pathways. The cyclo-oxygenase metabolites characterized as prostanoids have been implicated in the aetiology of inflammatory bowel diseases. Several of these long-chain unsaturated fatty acids, notably prostaglandin E2 (PGE2), have potent pro-inflammatory properties and can alter intestinal motility, fluid secretion and electrolyte transport1. These arachidonate metabolites could thus be involved in inflammatory diseases of the intestine and underlie the associated diarrhoea in diseases such as ulcerative colitis. In patients with active ulcerative colitis, highe levels of prostaglandin-like material could be detected in the stols2, with increased cyclo-oxygenase activity in vitro in rectal biopsies3. In other studies using radioimmunoassay techniques, elevated accumulation of PGE2 as well as thromboxane B2 (TXB2) and the prostacyclin breakdown product, 6-4,ox5o-PGF1 α in 24 h cultures of rectal mucosa biopsies were determined while studies in vivo using rectal dialysis procedures likewise indicated enhanced formation of PGE2 in patients with active ulcerative colitis6.
KeywordsArachidonic Acid Ulcerative Colitis Active Ulcerative Colitis Lipoxygenase Product Lipoxygenase Enzyme
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- 1.. Whittle BJR, Vane JR. Prostacyclin, thromboxanes and prostaglandins. Actions and roles in the gastro-intestinal tract. In: Progress in Gastroenterology, eds. G.B. Jerzy-Glass, P. Sherlock, Grune & Stratton, New York, pp. 3–30 (1983).Google Scholar
- 6.. Rampton DS, Sladen GE, Youlten LJF. Rectal mucosal prostaglandin E release and its relation to disease activity, electrical potential difference,- and treatment in ulcerative colitis. Gut, 21: 591 (1980).Google Scholar
- 13.. Boughton-Smith NK, Hawkey CJ, Whittle BJR. 1.piosynthesis of lipoxygenase and cyclo-oxygenase products from E CJ-arachidonic acid by human colonic mucosa. Gut 24: 1176 (1983).Google Scholar
- 17.. Azad Khan AK, Truelove SC, Aronson JK. The disposition and metabolism of sulphasalazine (salicylazosulphapyridine) in man. Br J Clin Pharmac. 13: 532 (1982).Google Scholar
- 18.. Higgs GA, Flower RJ, Vane JR. A new approach to anti–inflammatory drugs. Biochem. Pharmacol. 28: 1959 (1979).Google Scholar
- 19.. Salmon JA, Flower RJ. Prostaglandins and related compounds, in “Hormones in Blood”, Gray, C.H. and James, V.H.T. ed., Academic Press, New York (1979).Google Scholar
- 20.. Stenson WF, Lobos E. Inhibition of platelet thromboxane synthetase by sulfasalazine. Biochem. Pharmac. 32: 2205 (1983).Google Scholar
- . Robert A, Nezamis J, Lancaster C, Hanchar AJ. Cytoprotection by prostaglandins in rats - prevention of gastric necrosis produced by alcohol, HCL, NaOH, hypertonic NaCI and thermal injury. Gastroenterology, 77: 433 (1979).Google Scholar
- 28.. Hoult JRS, Moore PK. Sulphasalazine, a potent inhibitor of prostaglandin 15-hydroxy dehydrogenase: possible basis for therapeutic action in ulcerative colitis. Br J Pharmac. 64: 6 (1978).Google Scholar
- . Schlenker T, Peskar BM. Dual effect of sulphasalazine on colonic prostaglandin synthetase. Lancet ii: 815 (1981).Google Scholar
- 33.. Bennett A, Hensby CN, Sanger GJ, Stamford IF. Metabolites of arachidonic acid formed by human gastrointestinal tissues and their actions on the muscle layers. Br J Pharmac. 74: 435 (1981).Google Scholar
- 40.. Boughton-Smith NK, Hawkey CJ, Whittle BJR. Sulphasalazine and the inhibition of thromboxane synthesis in human colonic mucosa. Br J Pharmac. 80: 604P (1983).Google Scholar