Rebamipide prevents indomethacin-induced gastric mucosal lesion formation by inhibiting neutrophil activation in rats

Murakami, Kazunori; Okajima, Kenji; Harada, Naoaki; Liu, Wenge; Johno, Masayoshi; Okabe, Hiroaki

doi:10.1016/s0016-5085(98)80960-8

Cited by 36 publications

(52 citation statements)

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“…The mechanisms of anti-ulcer and cytoprotective actions of rebamipide are mainly divided into the following 3 types: 1) acceleration of ulcer healing based on the induction of prostaglandin synthesis via COX-2 expression (30 -32) and its receptor (33) and up-regulation of growth factor and its receptors such as epidermal growth factor (EGF) (34), vascular endothelial growth factor (VEGF) (35), and hepatocyte growth factor (HGF) (36); 2) cytoprotective activities such as induction of mucus secretion (37); 3) anti-inflammatory activities such as free-radical scavenging effect (38 -40), inhibition of neutrophil activation, and migration (41,42) and inhibition of cytokines production from leukocytes (43).…”

Section: Introductionmentioning

confidence: 99%

Prophylactic Effect of Rebamipide on Aspirin-Induced Gastric Lesions and Disruption of Tight Junctional Protein Zonula Occludens-1 Distribution

et al. 2008

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Abstract. Aspirin and nonsteroidal anti-inflammatory agents are known to induce gastroduodenal complications such as ulcer, bleeding, and dyspepsia. In this study, we examined the prophylactic effect of rebamipide, an anti-ulcer agent with free-radical scavenging and antiinflammatory effect, on acidified aspirin-induced gastric mucosal injury in rats. In addition, we investigated the mucosal barrier functions disrupted by aspirin. Oral administration of acidified aspirin resulted in linear hemorrhagic erosions with increasing myeloperoxidase activity and thiobarbituric acid-reactive substance concentrations in the gastric mucosa. Rebamipide suppressed these acidified aspirin-induced gastric lesions and inflammatory changes significantly, and its protective effect was more potent in the case of repeated (twice daily for 3 days) treatment than single treatment before aspirin administration. Immunostaining of zonula occludens (ZO)-1, one of the tight junctional proteins, was strengthened in rat gastric mucosa after repeated administration of rebamipide. In addition, aspirin induced the increasing transport of fluorescine isothiocyanate-labeled dextrans with localized disruption and decreased expression of ZO-1 protein on rat gastric mucosal cell line RGM-1. Rebamipide effectively prevented aspirin-induced permeability changes and disruption of ZO-1 distribution. These results suggest that rebamipide protects against aspirin-induced gastric mucosal lesions by preserving gastric epithelial cell-to cell integrity in addition to the anti-inflammatory effects.

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Section: Introductionmentioning

confidence: 99%

Prophylactic Effect of Rebamipide on Aspirin-Induced Gastric Lesions and Disruption of Tight Junctional Protein Zonula Occludens-1 Distribution

et al. 2008

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“…It is known to have preventative effects against various acute experimental gastric mucosal lesions and to accelerate the healing of gastric ulcers. Increased mucous secretion, 7) enhanced generation of endogenous prostaglandins, 8) suppression of neutrophil function, 9) inhibition of inflammatory cytokines, 10) and scavenging of oxygen free radicals 11) are known to be important effects of rebamipide in the stomach. Likewise, protective effects of rebamipide in the mucosa of the small intestine have been reported.…”

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confidence: 99%

Rebamipide Attenuates 5-Fluorouracil-Induced Small Intestinal Mucositis in a Mouse Model

Kim

Moon

et al. 2015

Biological & Pharmaceutical Bulletin

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5-Fluorouracil (5-FU)-induced intestinal mucositis is one of the most common morbidities in chemother-apy and involves the reactive oxygen species (ROS) system, apoptosis, and inflammatory cytokines. Rebamipide exerts a mucosal-protective effect, mediated through several mechanisms. The aim of this study was to evaluate the effects of rebamipide in 5-FU-induced mouse small-intestinal mucositis. BALB/c mice were assigned randomly to four groups; (1) control group (n 10; receiving saline orally for 6 d), (2) Key words mucositis; 5-fluorouracil; small intestine; rebamipide 5-Fluorouracil (5-FU) is a cytostatic agent that has been used widely in the treatment of various solid tumors for more than 20 years. It is still considered to be among the most effective anti-neoplastic agents in advanced colorectal cancer and malignancies of the head and neck.1) Many non-chromatographic and chromatographic methods for the quantitation of 5-FU, related pro-drugs, and metabolites in biological matrices have been developed over the last 30 years to support preclinical and clinical studies.2) Nevertheless, 50-80% of patients who undergo 5-FU chemotherapy show clinical manifestations of mucositis, symptoms of which include severe diarrhea.2) Its incidence in patients who underwent standarddose chemotherapy was 40%, while it approached 100% in patients treated with high-dose chemotherapy.3)The pathophysiological mechanism of 5-FU-induced mucositis comprises five phases 4)

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“…Rebamipide is a drug of great interest from an antiinflammation viewpoint, because in addition to having an anti-inflammatory affect, it effectively promotes mucin production. These actions have been shown to have inhibitory effects in an experimental model of gastritis 36 , to cause inhibition of inflammatory cell infiltration of gastric mucosa 37 , and to inhibit an inflammatory cytokine …”

Section: Discussionmentioning

confidence: 99%

Improvements in Signs and Symptoms of Dry Eye after Instillation of 2% Rebamipide

et al. 2015

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Purpose: Because dry eye greatly reduces quality of life, this study aimed to examine rebamipide instillation in patients with dry eye and assess the improvement of signs and symptoms as evaluated with the Ocular Surface Disease Index, which is the most popular index and is highly reliable. Methods:From June 2013 through January 2014, we examined 50 eyes of 25 patients with dry eye (6 men and 19 woman) at our institution. Dry eye was diagnosed on the basis of the presence of symptoms, tear dynamics, and ocular surface abnormalities according to the Japanese criteria for dry eye. Before being enrolled, all patients underwent ocular surface health assessment, including history interviews, and completed the Ocular Surface Disease Index questionnaire. Patients received 2% rebamipide ophthalmic solution 4 times daily for 4 weeks. Signs and symptoms were analyzed before and 4 weeks after rebamipide administration. Tear dynamics, tear break-up time, and ocular surface abnormalities were measured and compared between before and 4 weeks after rebamipide administration. Results:Of the 25 patients, 9 had definite dry eye and 16 had probable dry eye. Tear break-up time and the fluorescein staining score significantly improved after 4 weeks. However, no significant change was observed for the Schirmer test I and the lissamine green staining score. Conclusions:The administration of 2% rebamipide 4 times daily for 4 weeks improves the signs and symptoms of dry eye and improves patients' quality of life. (J Nippon Med Sch 2015; 82: 229 236)

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Rebamipide prevents indomethacin-induced gastric mucosal lesion formation by inhibiting neutrophil activation in rats

Cited by 36 publications

References 0 publications

Prophylactic Effect of Rebamipide on Aspirin-Induced Gastric Lesions and Disruption of Tight Junctional Protein Zonula Occludens-1 Distribution

Prophylactic Effect of Rebamipide on Aspirin-Induced Gastric Lesions and Disruption of Tight Junctional Protein Zonula Occludens-1 Distribution

Rebamipide Attenuates 5-Fluorouracil-Induced Small Intestinal Mucositis in a Mouse Model

Improvements in Signs and Symptoms of Dry Eye after Instillation of 2% Rebamipide

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