Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038358 (gastric ulcer)
 5,179 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanism of the inhibitory action of rebamipide, a new mucosal protective drug, was studied using rats with diethyldithiocarbamate-induced gastric antral ulcers. Rebamipide reduced ulcer formation and inhibited the elevation in lipid peroxide concentration in the gastric mucosa. Rebamipide inhibited both luminol- and lucigenin-dependent chemiluminescence of neutrophils activated by formyl-methionyl-leucyl-phenylalanine. Rebamipide did not alter the reduction of cytochrome c induced by the xanthine-xanthine oxidase system or the NADPH-dependent microsomal lipid peroxidation in the liver. These findings suggest that rebamipide prevents diethyldithiocarbamate-induced gastric ulcer formation by inhibiting neutrophil activation.
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PMID:Antiulcer mechanism of action of rebamipide, a novel antiulcer compound, on diethyldithiocarbamate-induced antral gastric ulcers in rats. 131 72

Our objectives were to determine whether rebamipide, a unique antiulcer agent, would inhibit adhesive reactions between neutrophils and endothelial cells as well as the production of active oxygen species from neutrophils elicited by an extract of H. pylori. A water extract of H. pylori that was prepared from biopsy materials obtained from a patient with gastric ulcer increased the surface expression of CD18 on human neutrophils isolated from peripheral blood, the adhesion of neutrophil-endothelial cells, and the production of active oxygen species by neutrophils. Rebamipide, at concentrations of 10(-5) and 10(-6) M, reduced the adherence of neutrophils to endothelial cells as well as the CD18 expression on neutrophils induced by this bacterial extract. Rebamipide also inhibited the production of active oxygen species from neutrophils stimulated by H. pylori extract. These results suggest that rebamipide protects against the gastric mucosal inflammation associated with H. pylori by inhibiting neutrophil function.
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PMID:Rebamipide protects against activation of neutrophils by Helicobacter pylori. 865 44

Rebamipide which is used as a drug for gastritis and stomach ulcer has large capability for OH radical scavenging. It is expected that rebamipide has protective effect against ionizing radiations. The present paper deals with protective effect of rebamipide for cultured mammalian cells exposed to ionizing radiations. As rebamipide is insoluble in water, three solvents were used to dissolve. Rebamipide dissolved in dimethyl sulfoxide (DMSO), dimethyl formamide (DMFA) and 0.02 N NaOH was added to the cells in Eagle's minimum essential medium (MEM) supplemented with 10% fetal calf serum and the cells were irradiated with X-rays. After irradiation, the cells were trypsinized, plated in MEM with 10% fetal calf serum and incubated for 7 days in a CO2 incubator to form colonies. Rebamipide dissolved in 0.02 N NaOH exhibited the protective effect expected its OH radical scavenging capability. However, the protective effect of rebamipide dissolved in DMSO was about half of that expected by its radical scavenging capability and that of rebamipide dissolved in DMFA was not observed. Uptake of rebamipide labeled with 14C increased with increasing contact time with rebamipide. These rebamipide mainly distributed in nucleous rather than cytoplasm.
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PMID:[Protection of cultured mammalian cells by rebamipide]. 924 42

Rebamipide, a gastroprotective drug, is a compound selected from over 500 amino acid analogs of 2(1H)-quinolinone tested for gastroprotective action and for efficacy to heal experimental gastric ulcers. This drug stimulates prostaglandin generation in gastric mucosa and improves not only the speed but also the quality of ulcer healing. In addition, it protects the gastric mucosa against acute injury caused by various noxious and ulcerogenic factors. Based on these experimental results, rebamipide had been subsequently tested in several clinical trials and approved in Japan for therapeutic use in patients with gastric ulcers and patients with acute gastritis. The main purpose of developing this type of drug was to improve the quality of ulcer healing, especially in that antisecretory drugs lack this advantage. In a preliminary clinical study, rebamipide improved the quality of gastric ulcer healing and reduced future ulcer recurrence. A number of basic research studies have been performed to clarify the mechanisms of rebamipide's action. These studies demonstrated unique properties of rebamipide and convincingly showed that it increases gastric mucus glycoprotein components, stimulates migration and proliferation of wounded epithelial cell monolayers, increases expression of epidermal growth factor and its receptor in normal and ulcerated gastric mucosa, and scavenges active oxygen radicals. The drug also attenuates the activity of neutrophils and the production of inflammatory cytokines stimulated by NSAIDs and/or H. pylori. Therefore, rebamipide can contribute to the management of patients who are taking NSAIDs or are infected with H. pylori. The inhibition of immunoinflammatory responses by rebamipide in H. pylori-infected patients may prevent development of gastritis, peptic ulcer disease, its recurrence, and possibly gastric cancer. Moreover, rebamipide may enhance eradication of H. pylori-infection using standard eradication therapy. Further studies are needed to clarify these possible advantages of rebamipide.
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PMID:Rebamipide: overview of its mechanisms of action and efficacy in mucosal protection and ulcer healing. 975 20

Rebamipide is the first anti-gastric ulcer and antigastritis drug that not only increases endogenous prostaglandin in gastric mucosa but also scavenges oxygen-derived free radicals and inhibits their production. In the present paper, we have reviewed the antioxidative and antiinflammatory properties of rebamipide mainly demonstrated by in vitro studies. The study, using the electron paramagnetic resonance (EPR) spin trapping technique, showed that superoxide production was inhibited by rebamipide when isolated human neutrophils were stimulated with opsonized zymosan or Helicobacter pylori water extract in a dose-dependent manner. Chemiluminescence generated from neutrophils activated by H. pylori or formyl-methionyl-leucyl-phenylalanine was also decreased by the treatment with rebamipide. Rebamipide, at concentrations of 10(-5) and 10(-6) M, reduced the adherence of neutrophils to endothelial cells as well as the CD18 expression on neutrophils induced by H. pylori water extract. The EPR study also demonstrated the direct hydroxyl radical scavenging activity of rebamipide, and a kinetic study showed that the second-order rate constant for the reaction between rebamipide and hydroxyl radical was 2.24 x 10(10) M(-1)/s(-1). The inhibitory effect of rebamipide on lipid peroxidation induced by a free radical initiator was also demonstrated by the in vitro system using rat gastric mucosal homogenates. These data indicate that rebamipide offers a potential for protection against reactive oxygen- and activated neutrophil-associated gastric mucosal injury by scavenging hydroxyl radical and inhibiting neutrophil activation or lipid peroxidation.
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PMID:In vitro studies indicating antioxidative properties of rebamipide. 975 24

Rebamipide, a gastroprotective drug developed in Japan, accelerates ulcer healing and reduces recurrence of experimental gastric ulcers. We examined the effects of rebamipide, given during healing of human gastric ulcers infected with Helicobacter pylori, on the quality of ulcer healing and ulcer recurrence. Sixty H. pylori-positive patients with gastric ulcers were randomly allocated to three treatment groups: group O (N = 20) received 20 mg of omeprazole every day for eight weeks, group OR (N = 20) received the same dose of omeprazole and 300 mg of rebamipide three times a day for eight weeks, and group OA (N = 20) received the same dose of omeprazole for eight weeks and 1500 mg of amoxicillin three times a day for the first two weeks. After this treatment was completed no other medication was given. Endoscopic examinations were performed at the end of therapy (for healing rate), one month later (for rate of H. pylori eradication) and every three months for follow-up (for ulcer recurrence rate). At the end of therapy, biopsy specimens were taken from the gastric ulcer scar and examined under the microscope for neutrophil and mononuclear cell infiltration. The ulcer healing rate of the three groups was almost the same; H. pylori in group OA was 65% and that of the other two groups was 0%. The number of patients with a flat ulcer scar pattern (good quality of ulcer healing) was increased and the neutrophil infiltration was significantly improved in groups OR and OA compared to group O. The ulcer recurrence rate was significantly lower in group OA and group OR than in group O. In conclusion, rebamipide is almost equipotent to amoxicillin plus omeprazole for the reduction of ulcer recurrence. The decreased recurrence rate by rebamipide may be due to improvement of the quality of ulcer healing, reflected as in the suppression of inflammatory cell infiltration in the scar, which results from either cure of H. pylori infection and/or treatment with a gastroprotective drug such as rebamipide.
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PMID:Rebamipide prevents recurrence of gastric ulcers without affecting Helicobacter pylori status. 975 34

Prostaglandin E2 (PGE2) plays an important role in the regulation of gastric mucus secretion. We have previously shown that the prostaglandin EP4 receptor (EP4) gene is abundantly expressed in gastric mucus-producing cells. Furthermore, we have shown that EP4 is present in a rat normal gastric mucosal cell line (RGM1) and that PGE2 increases mucus secretion from these cells via EP4. Rebamipide, an anti-gastric ulcer agent, has been reported to promote gastric PGE2 production and mucus secretion. However, it is unclear whether rebamipide influences mucus secretion by altering expression of the EP4 gene. Therefore, we tested the effect of rebamipide on EP4 gene expression in the gastric mucosa. Seven-week-old Wistar rats received oral rebamipide (100 mg/kg) with and without water-immersion restraint stress (WRS). All rats were killed, and their gastric tissues were used to investigate the expression of mRNA for EP4 and cyclooxygenase types 1 and 2. The thickness of the gastric mucus layer was also measured. The effect of rebamipide on EP4 gene expression and PGE2 production in RGM1 cells was also investigated in vitro. Furthermore, the effect of PGE2 on cyclic adenosine monophosphate (cAMP) production by RGM1 cells with or without rebamipide was studied. Oral rebami-pide significantly increased EP4 gene expression in the gastric antrum but not in the corpus after WRS. Furthermore, it increased surface mucus thickness and suppressed ulcer formation in the gastric mucosa after WRS. In vitro, rebamipide significantly augmented EP4 gene expression in RGM1 cells, and PGE2 significantly increased the cAMP production by RGM1 cells incubated with rebamipide. Rebamipide promotes EP4 gene expression and may consequently increase the gastric mucus secretion via EP4 receptors in the rat antral mucosa.
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PMID:Effect of rebamipide on prostaglandin EP4 receptor gene expression in rat gastric mucosa. 1088 27

In this study, we examined the effect of rebamipide, a mucoprotective drug, on gastric ulcer healing in Mongolian gerbils infected with H. pylori. Male Mongolian gerbils were inoculated with H. pylori or vehicle alone 12 hr after the production of an acetic acid-induced gastric ulcer. On day 5, the gerbils inoculated with H. pylori were divided into three groups and fed rebamipide-containing diet (0.038%, 60 mg/kg, or 0.0038%, 6 mg/kg), or standard laboratory chow. The gerbils inoculated with the vehicle were fed standard laboratory chow throughout the experiment. The gerbils were killed on day 5, 15, or 30 after ulcer production, and removed stomachs were subjected to calculation of ulcer size, culture for H. pylori, and measurement of myeloperoxidase activity, a marker for neutrophil infiltration, in ulcerated tissue. Apoptotic and proliferating cells of gastric epithelium in ulcer margins were detected by the in situ DNA nick end-labeling method and immunohistochemical staining for 5-bromo-2'-deoxyuridine (BrdU), respectively. Rebamipide did not affect colonization levels of H. pylori. Infection with H. pylori did not affect ulcer size by day 5 but significantly delayed ulcer healing by days 15 and 30, accompanied by an increase in the number of apoptotic cells, a decrease in the number of BrdU-positive cells, and an increase in myeloperoxydase activity. Rebamipide prevented delay of ulcer healing and abolished these effects of H. pylori on cell kinetics and neutrophil infiltration. In conclusion, rebamipide may prevent the delay of acetic acid-induced gastric ulcer healing caused by H. pylori through modulating cell kinetics and inhibiting neutrophil infiltration.
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PMID:Rebamipide prevents delay of acetic acid-induced gastric ulcer healing caused by Helicobacter pylori infection in Mongolian gerbils. 1214 20

Rebamipide is an antiulcer drug capable of various actions including the induction of cyclooxygenase-2 (COX-2). In this study, we investigated the effect of rebamipide on gastric ulcer healing in COX-2-deficient mice. Wild-type (N=34) and COX-2-deficient mice (N=28) with gastric ulcers were administered 30 mg/kg of rebamipide or the vehicle. Ulcerous tissues were subjected to measurements of ulcer size, immunohistochemical staining of CD31 (an endothelial cell marker), and mRNA levels. COX-2 deficiency delayed ulcer healing and inhibited angiogenesis and bFGF mRNA expression in the granulation tissue. In wild-type mice, rebamipide accelerated ulcer healing and increased COX-2 mRNA expression. In COX-2-deficient mice, rebamipide prevented delayed ulcer healing and reversed the inhibition in angiogenesis and bFGF mRNA expression. The effect of rebamipide on the enhancement of ulcer healing, angiogenesis, and induction of bFGF expression was more prominent in wild-type mice than in COX-2-deficient mice. In conclusion, rebamipide may accelerate gastric ulcer healing through both COX-2-dependent and COX-2-independent mechanisms.
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PMID:Rebamipide reduces delay in gastric ulcer healing in cyclooxygenase-2-deficient mice. 1618 23

Mucosal inflammation is a crucial factor for the recurrence of peptic ulcer. In this study, we examined the effect of rebamipide on neutrophils infiltration, lipid peroxidation, and antioxidative enzyme activities in the recurrence of experimental gastric ulcer. Ulcer recurrence was examined at 60, 100, and 140 days after production of acetic acid-induced gastric ulcers in rats. Gastric neutrophil infiltration, lipid peroxidation, and antioxidative enzyme activities were determined by analyses of myeloperoxidase (MPO) activity, thiobarbituric acid reactive substance (TBARS) levels, and glutathione peroxidase (GSHpx) and superoxide dismutase (SOD) activities in the ulcer region, respectively. The effect of rebamipide, an antigastric-ulcer agent, on ulcer recurrence was assessed following oral administration at 60 mg/kg/day from day 20. In the control and rebamipide groups, gastric ulcer indices were reduced on day 100 compared with day 60; however, increases were observed on day 140, indicating ulcer recurrence. In the rebamipide group, the ulcer index was smaller than in the control group at each time point and the effect was significant on day 140. Although marked elevation of MPO activities was observed in the control group during the experiment, no significant elevations were seen in the rebamipide group on days 100 and 140. TBARS levels were significantly elevated in the control group on day 140, but not in the rebamipide group. Rebamipide suppressed the decrease in GSHpx activity on day 60. These results suggest that lipid peroxidation of gastric tissue mediated by free radicals from neutrophils is responsible for the recurrence of acetic acid-induced gastric ulcers in rats, and that the elimination of free radicals by rebamipide may contribute to the reduction of severity in ulcer recurrence.
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PMID:Rebamipide reduces recurrence of experimental gastric ulcers: role of free radicals and neutrophils. 1618 27


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