Effects of NSAIDs on cryoprobe‐induced gastric ulcer healing in rats

Abstract

The administration of traditional NSAIDs is associated with a three-fold increase in the risk of development of signi®cant gastrointestinal complications, depending on previous risk factors. 1±3 Cross-sectional studies indicate that gastric or duodenal ulcers are present in 10±25% of patients on long-term NSAIDs.2, 4, 5 Most NSAIDinduced ulcers heal spontaneously without treatment, with or without discontinuation of NSAID therapy. 6 However, a small proportion of the ulcers produced by NSAIDs progress to clinically serious events, such as a perforation or a bleeding ulcer. 2,7 The critical factors in the pathogenesis of these serious events are unknown, but the particular type and dose of NSAID taken, the location of the ulcer in relation to vessels and the effect of NSAIDs on platelet function may be important, as well as whether there is adequate healing of ulcers. 8±11One of the primary mechanisms responsible for the gastrointestinal toxicity produced by NSAIDs is believed to be suppression of endogenous gastric prostaglandin synthesis. Another is the`topical' effect, which may involve a surface membrane phospholipid interaction and/or an effect to uncouple mitochondrial oxidative phosphorylation.12±16 With the identi®cation 17 of two distinct isoforms of cyclooxygenase (COX) responsible for prostaglandin synthesis, COX-1 and COX-2, their roles in the pathogenesis of NSAID-induced gastroduodenal ulcers have been debated. In normal gastric tissue, high levels of COX-1 are expressed, whereas SUMMARY Background: Failure of ulcer healing may be critically important to the development of serious gastrointestinal complications in patients on long-term NSAIDs. Aim: To determine the effect of indometacin, celecoxib, a cyclooxygenase-2-speci®c inhibitor, and nabumetone, a pro-drug, on ulcer healing rates in the rat. Methods: Gastric ulcers were induced using a cryoprobe. An NSAID or a vehicle control was administered to groups of eight rats for 3 or 6 days (2 mg/kg indometacin, 9 mg/kg celecoxib or 40 mg/kg nabumetone). The ulcer area was measured and epithelial proliferation at the ulcer margins was measured histochemically. The effect of the drugs on intestinal prostaglandin levels was also assessed.

Analyzing the influence of gastric intestinal metaplasia on gastric ulcer healing in Helicobacter pylori–infected patients without atrophic gastritis

“…The mechanisms associated with GU healing and repair include epithelial cell proliferation, growth control, epidermal growth factors, angiogenesis and inhibition of acid secretion [12, 13, 28, 29]. Although our original hypothesis was that cell hyperproliferation in IM might influence GU healing, we found that there was no significant difference in cell proliferation Ki-67 stain index between the IM group and the no IM group.…”

Nonsteroidal Anti-Inflammatory Drug-Activated Gene-1 Plays a Role in the Impairing Effects of Cyclooxygenase Inhibitors on Gastric Ulcer Healing

“…However, literature data on celecoxib are conflicting. For instance, Tibble et al (2001) found that celecoxib, administered for 6 days at 9 mg/kg/day, delayed ulcer healing in rats. Likewise, a 15-day treatment with celecoxib at 1.8 mg/kg twice daily impaired ulcer repair in rats (Berenguer et al, 2002).…”

Aspirin Can Elicit The Recurrence of Gastric Ulcer Induced with Acetic Acid in Rats

“…Gastric mucus, gastric mucosal blood flow (GMBF) and mucosal PGE 2 Gastric mucus was determined according to the previous method [17] with a slight modification. Briefly, stomach was cut along lesser curvature.…”

“…NSAIDs 206 are one kind of the most frequently used drugs world wide [1], aspirin is one of them. Cross-sectional studies indicate that gastric or duodenal ulcers are present in 10-25% of patients on long-term NSAIDs [2]. Furthermore, continuing usage of NSAIDs often results in the recurrence of gastric ulcer [3].…”