Are prostaglandins cytoprotective in the human large intestine?—the effect of indomethacin on rectal mucosal function and prostaglandin E2 releasein vivo

Abstract

To test the hypothesis that prostaglandins are cytoprotective in the human large intestine, we investigated the effect of withdrawal of treatment with indomethacin suppositories on bowel habit and on rectal mucosal electrolyte transport and prostaglandin production in 8 patients taking such treatment for rheumatological disorders. Discontinuation of indomethacin doubled rectal mucosal prostaglandin E2 release (p less than 0.05) measured by in vivo rectal dialysis. Although there was no significant overall change in stool frequency, stool consistency, rectal bleeding or sodium absorption (also assessed by rectal dialysis), sigmoidoscopic appearance (p = 0.05), rectal mucosal potential difference (p less than 0.05) and potassium transport (p = 0.01) each reverted towards normal on indomethacin withdrawal. These results accord with the theory that, as in the upper gastrointestinal tract, prostaglandins may play a role in the maintenance of rectal mucosal structure and function.

Systematic review: the lower gastrointestinal adverse effects of non‐steroidal anti‐inflammatory drugs

“…The initial search strategy identified a total of 930 references. We accepted 179 titles and abstracts for article retrieval and further screening; of these, 46 papers met our explicit inclusion and exclusion criteria 10–55 Figure 1. depicts the results of the screening process.…”

“…Twenty‐two studies 10, 14, 16, 20–23, 26, 33, 35, 39–42, 44, 45, 47–50, 52, 55 investigated lower GI integrity, the largest single category. Seven studies 10–12, 27, 38, 45, 51 used visualization approaches. Twenty studies looked at clinical outcomes: 11 lower GI bleeding, 19, 24, 30, 31, 34, 36, 37, 51, 53, 54 two lower GI perforation 32, 54 and seven diverticular disease 13, 15, 18, 28, 29, 43, 46 .…”

Paradox of simultaneous intestinal ischaemia and hyperaemia in inflammatory bowel disease

“…More recently, authors have noted a higher than expected use of NSAIDs among patients admitted to the hospital for flares of IBD [140], leading some physicians to recommend that IBD patients strictly avoid use of NSAIDs [135,141]. The mechanism by which NSAIDs may provoke inflammatory bowel disease is not clear, but may involve a mechanism of altered arachidonic acid metabolism similar to that of NSAID‐induced enterocolitis that is not related to IBD [142–145]. Some prostaglandins, end products of the cyclooxygenase pathway, serve a protective role in the gut [146–149] and NSAIDs inhibit their formation.…”

Indomethacin worsens and a leukotriene biosynthesis inhibitor accelerates mucosal healing in rat colitis

“…Recently, with the aid of in vkvo rectal dialysis, lurninal levels of LTB4 were positively correlated to inflammatory bowel disease activity, these levels falling in patients responding to treatment and remaining elevated in those not responding (Lauritsen et al 1986). Furthermore, drugs that selectively inhibit prostaglandin production, i. e., indornethacin and flurbiprofen, provide no therapeutic benefit to patients with inflammatory bowel disease and may actually aggravate colonic mucosal inflammation in the face of reduced levels of prostaglandins (Gould et al 1984 ;Levy and Gaspar 1975;Rampton and Barton 1984;Rampton and Sladen 1984). This led to the hypothesis that generation (through the 5-ligoxygenase pathway) of leukotrienes may thus be injurious to intestinal rnucssa, while generation (through the cyclooxygenase pathway) of prostaglandins may provide a rnucosd protective role (Fedor& et al 1990;Psaila et al 1986;Robert et d. 1979; Wallace et al 1985).…”