Rebamipide, novel prostaglandin-inducer, accelerates healing and reduces relapse of acetic acid-induced rat gastric ulcer comparison with cimetidine

Arakawa, Tetsuo; Watanabe, Toshio; Fukuda, Takashi; Yamasaki, K.; Kobayashi, Kenzo

doi:10.1007/bf02063257

Cited by 70 publications

(43 citation statements)

References 11 publications

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“…There are only a few reports on the recurrence of ulcer after healing in experimental models. Arakawa et al [23,24] reported that the cumulative recurrence rate was about 30% (cumulative nonrecurrence rate 70%) on the 90th day after ulcer induction in the acetic acid-ulcer model. The differences in the cumulative recurrence rates between Arakawa's and this study might depend on the difference in the intensity of the ulceration, as on the 150th their cumulative healing rate was high in comparison with that of this study.…”

Section: Discussionmentioning

confidence: 99%

“…But it remains unclear why prolonged treatment with FRG-8813 did not cause the rebound hyperacidity, as famotidine and cimetidine did not induce hypergastrinemia either. On the other hand, it has also been postulated that a decrease in gastric defensive factors resulted in ulcer recurrence [11], and that treatment with a gastroprotective drug, increasing the levels of gastric defense factors, and H 2 -receptor antagonist is beneficial for obtaining a good QOUH and reducing ulcer recurrence [23]. Indeed, for prevention of ulcer recurrence a gastroprotective drug was used clinically with a H 2 -receptor antagonist, and a lower recurrence rate was shown for ulcers healed with combination therapy than for those treated with the H 2 -receptor antagonist alone [3,14].…”

Section: Discussionmentioning

confidence: 99%

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Effect of FRG-8813, a New-Type Histamine H2-Receptor Antagonist, on the Recurrence of Gastric Ulcer after Healing by Drug Treatment in Rats

Ajioka

Miyake²,

Matsuura³

2000

Pharmacology

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We investigated the recurrence of ulcers in rats after treatment with FRG-8813, (±)-2-(furfurylsulfinyl)-N-[4- [4-(piperidinomethyl)-2-pyridyl] oxy-(Z)-2-butenyl] acetamide, a novel histamine H₂-receptor antagonist. Chronic gastric ulcers were induced by serosa-searing with a hot metal bar, and the ulcer healing and recurrence after treatment with FRG-8813 or famotidine were evaluated by endoscopy for 160 days. At the dose of 30 mg/kg p.o., once daily, the treatment with FRG-8813 or famotidine for 60 days, which was stopped earlier if the ulcer had healed, accelerated the ulcer healing significantly. A subsequent follow-up study on the healed rats showed that the cumulative recurrence rate of rats healed by FRG-8813 was lower than that of naturally healed rats or rats healed by famotidine. In many cases of rats healed by FRG-8813, the regenerated mucosa was normal in contrast with the control of famotidine-healed animals. The mucosal regeneration index of the gastric ulcer after 10 days’ administration of FRG-8813 was significantly higher than that obtained with famotidine. After cessation of the treatment with famotidine for 7 days, rebound hyperacidity was induced; but such rebound did not occur with FRG-8813. Considering the low recurrence rate of ulcers after FRG-8813 treatment, we suggest that FRG-8813 treatment may provide additional benefits in peptic ulcer therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Effect of FRG-8813, a New-Type Histamine H2-Receptor Antagonist, on the Recurrence of Gastric Ulcer after Healing by Drug Treatment in Rats

Ajioka

Miyake²,

Matsuura³

2000

Pharmacology

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“…Its mechanism of action is not fully understood, though it appears to stimulate mucus secretion and PG synthesis [121] and to scavenge oxygen-derived free radicals [6] . It has been shown to significantly reduce the severity of NSAID-induced enteropathy in rats [122] .…”

Section: Nsaid-enteropathymentioning

confidence: 99%

Mechanisms, prevention and clinical implications of nonsteroidal anti-inflammatory drug-enteropathy

Wallace¹

2013

WJG

151

148

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This article reviews the latest developments in understanding the pathogenesis, detection and treatment of small intestinal damage and bleeding caused by nonsteroidal anti-inflammatory drugs (NSAIDs). With improvements in the detection of NSAID-induced damage in the small intestine, it is now clear that this injury and the associated bleeding occurs more frequently than that occurring in the stomach and duodenum, and can also be regarded as more dangerous. However, there are no proven-effective therapies for NSAIDenteropathy, and detection remains a challenge, particularly because of the poor correlation between tissue injury and symptoms. Moreover, recent studies suggest that commonly used drugs for protecting the upper gastrointestinal tract (i.e. , proton pump inhibitors) can significantly worsen NSAID-induced damage in the small intestine. The pathogenesis of NSAIDenteropathy is complex, but studies in animal models are shedding light on the key factors that contribute to ulceration and bleeding, and are providing clues to the development of effective therapies and prevention strategies. Novel NSAIDs that do not cause small in- FRONTIER

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“…[93][94][95][96][97] Penney et al 98) demonstrated that misoprostol reversed the delayed healing effect of aspirin via an effect on epithelial regeneration. Arakawa et al 99) examined the effects of rebamipide, a novel PG-inducer, on healing and relapse of acetic acid ulcers in rats. Arakawa found that rebamipide and rebamipide together with cimetidine resulted in a higher healing rate and a lower cumulative relapse rate compared to control groups.…”

Section: Mucosal Defensive Drugsmentioning

confidence: 99%

An Overview of Acetic Acid Ulcer Models —The History and State of the Art of Peptic Ulcer Research—

Okabe

Amagase

2005

Biological & Pharmaceutical Bulletin

207

166

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Four types of experimental chronic ulcer models, named acetic acid ulcer models, have been developed to examine the healing process of peptic ulcers, screen anti-ulcer drugs, and better evaluate the adverse effects of various anti-inflammatory drugs on the gastrointestinal mucosa. The model easily and reliably produces round, deep ulcers in the stomach and duodenum, allowing acetic acid ulcer production in mice, rats, Mongolian gerbils, guinea pigs, cats, dogs, miniature pigs, and monkeys. These ulcer models highly resemble human ulcers in terms of both pathological features and healing process. The models have been established over the past 35 years and are now used throughout the world by basic and clinical scientists. One of the characteristic features of acetic acid ulcers in rats is the spontaneous relapse of healed ulcers Ͼ100 d after ulceration, an endoscopically confirmed phenomenon. Indomethacin significantly delays the healing of acetic acid ulcers, probably by reducing endogenous prostaglandins and inhibiting angiogenesis in ulcerated tissue. Helicobacter pylori significantly delays healing of acetic acid ulcers and causes relapse of healed ulcers at a high incidence in Mongolian gerbils. Anti-secretory drugs (e.g. omeprazole), prostaglandin analogs, mucosal defense agents (e.g. sucralfate), and various growth factors all significantly enhance healing of acetic acid ulcers. Gene therapy with epidermal growth factor and vascular endothelial growth factor applied to the base of acetic acid ulcers in rats is effective in enhancing ulcer healing. Since an inhibitor of nitric oxide syntase prevents ulcer healing, nitric oxide might be involved in the mechanism underlying ulcer healing. We conclude that acetic acid ulcer models are quite useful for various studies related to peptic ulcers.

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Rebamipide, novel prostaglandin-inducer, accelerates healing and reduces relapse of acetic acid-induced rat gastric ulcer comparison with cimetidine

Cited by 70 publications

References 11 publications

Effect of FRG-8813, a New-Type Histamine H<sub>2</sub>-Receptor Antagonist, on the Recurrence of Gastric Ulcer after Healing by Drug Treatment in Rats

Effect of FRG-8813, a New-Type Histamine H<sub>2</sub>-Receptor Antagonist, on the Recurrence of Gastric Ulcer after Healing by Drug Treatment in Rats

Mechanisms, prevention and clinical implications of nonsteroidal anti-inflammatory drug-enteropathy

An Overview of Acetic Acid Ulcer Models<br>—The History and State of the Art of Peptic Ulcer Research—

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Rebamipide, novel prostaglandin-inducer, accelerates healing and reduces relapse of acetic acid-induced rat gastric ulcer comparison with cimetidine

Cited by 70 publications

References 11 publications

Effect of FRG-8813, a New-Type Histamine H<sub>2</sub>-Receptor Antagonist, on the Recurrence of Gastric Ulcer after Healing by Drug Treatment in Rats

Effect of FRG-8813, a New-Type Histamine H<sub>2</sub>-Receptor Antagonist, on the Recurrence of Gastric Ulcer after Healing by Drug Treatment in Rats

Mechanisms, prevention and clinical implications of nonsteroidal anti-inflammatory drug-enteropathy

An Overview of Acetic Acid Ulcer Models<br>&mdash;The History and State of the Art of Peptic Ulcer Research&mdash;

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An Overview of Acetic Acid Ulcer Models<br>—The History and State of the Art of Peptic Ulcer Research—