Effect of Rebamipide on Quality of Peptic Ulcer Healing in Rat

Abstract

The aim of this study is to elucidate the effects and the mechanism of rebamipide, omeprazole, and their combination treatment on quality of peptic ulcer healing (QOUH). Peptic ulcer models were induced by acetic acid exposure of the serosa of rat stomach. Forty Sprague-Dawley (SD) rats were divided randomly into four groups of ten rats each. Saline 2 ml/d (group 1), rebamipide 60 mg/kg/d (group 2), omeprazole 10 mg/kg/d (group 3) as well as its combination regimen (group 4) were administrated for 7 days. After sacrifice, size of the ulcer and focal layer structures were measured in vitro by miniature ultrasonic probe, and the mucosal sections were stained with hematoxylin and eosin (HE) for histological examination; the levels of interleukin (IL)-8/prostaglandin E(2) (PGE(2)) were evaluated by enzyme-linked immunosorbent assay (ELISA) and malondialdehyde (MDA) level was evaluated by thiobarbituric acid (TBA) method. Macroscopically, compared with the control group, the maximal diameters of the ulcers in the medication groups were significantly reduced (P < 0.05), and the layer echo structures of gastric wall were partially rebuilt. Histologically, ulcer range and inflammatory infiltration were less severe compared with the control group. In addition, mucosal MDA and IL-8 levels were significantly decreased, while PGE(2) level was significantly increased in the medication groups. Between the two monotherapy groups, there was no statistical difference in terms of PGE(2) and MDA levels. However, PGE(2) level was significantly increased, while MDA and IL-8 levels were significantly decreased in the combination group. Rebamipide as well as omeprazole and the combination regimen may improve QOUH through increasing the level of PGE(2), decreasing the levels of IL-8 and MDA in gastric mucosa, and this may potentially result in reduced recurrence of ulcer; moreover, the combination regimen was identified as having more antiulcer effects than monotherapy.

Can rebamipide and proton pump inhibitor combination therapy promote the healing of endoscopic submucosal dissection–induced ulcers? A randomized, prospective, multicenter study

“…19,20 A recent ani- mal study suggested that rebamipide might enhance the quality of ulcer healing by increasing levels of prostaglandin E 2 and decreasing levels of interleukin-8 and malondialdehyde. 21 Interestingly, in this study, the artificial ulcer healing rate was higher in the PPI and rebamipide combination group regardless of the initial ulcer size, whereas a previous smaller study suggested that this 4-week combination therapy was more effective than PPI alone for treating ulcers larger than 20 mm. 6 This discrepancy can be explained by the difference in the primary outcomes of each study.…”

“…11 Rebamipide not only can promote peptic ulcer healing but also can reduce its recurrence by improving quality of ulcer healing related to the inhibition of inflammatory responses. 11,21,29 In ESD-induced ulcers, it is unclear whether high quality of ulcer healing can reduce the recurrence of artificial ulcers. Although EMR-induced ulcers might heal faster, recur less often, or require shorter treatments than peptic ulcers, 3,30 further studies to investigate the effects of quality of ulcer healing in ESD-induced ulcers, which are usually larger and deeper than EMR-induced ulcers, should be conducted in the future.…”

Rebamipide does not protect against naproxen-induced gastric damage: a randomized double-blind controlled trial

“…Increased PG synthesis was previously suggested as a possible mechanism for mucosal protection of rebamipide [ 16 , 17 ]. If so, rebamipide should not have a protective effect in NSAID-induced gastric damage through modulation of PG synthesis, since NSAIDs block the activity of cyclooxygenases.…”

“…Rebamipide has been described as a GI mucosal protector agent with promising results in prophylaxis and treatment of GI ulcers caused by NSAIDs, H. pylori or endoscopic submucosal dissection [ 9 – 15 ]. Results from animal studies have suggested that the protective effects of rebamipide are attributable to stimulation of prostaglandin (PG) synthesis [ 16 , 17 ]. In healthy volunteers, concomitant administration of rebamipide 100 mg with ibuprofen 600 mg t.i.d.…”

Efficacy and Safety of Proton Pump Inhibitors (PPIs) Plus Rebamipide for Endoscopic Submucosal Dissection-induced Ulcers: A Meta-analysis

“…These actions increase the gastric mucosal blood flow at the ulcer margin, an important factor for ulcer healing, and accelerate the mucosal or submucosal reconstruction of damaged structures (24,26). A recent animal study suggested that treatment with rebamipide enhances the quality of ulcer healing by increasing the level of prostaglandin E2 and decreasing the levels of interleukin-8 and malondialdehyde (27). Previous studies have also reported that ulcer healing is associated with both the lesion size and tumor location.…”