Antiulcer mechanism of action of rebamipide, a novel antiulcer compound, on diethyldithiocarbamate-induced antral gastric ulcers in rats

Oginö, Kazuhíde; Hobara, Tatsuya; Ishiyama, H.; Yamasaki, K.; Kobayashi, Haruo; Izumi, Yukie; Oka, Shinji

doi:10.1016/0014-2999(92)90065-c

Cited by 88 publications

(60 citation statements)

References 32 publications

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“…The increased oxidative stress may be caused not only by an accelerated production of reactive oxygen species but also by a decreased scavenging ability of those molecules. Indeed, the development of DDC-induced antral lesions was prevented by pretreatment with SOD, a radical scavenger, and worsened by drugs that impair the antioxidative system (Ogino et al, 1992). In the present study, the severity of antral lesions induced by indomethacin plus paroxetine was significantly reduced by pretreatment with allopurinol, an inhibitor of oxyradical production, as well as SOD.…”

Section: Discussionsupporting

confidence: 51%

“…The pathogenesis of these lesions is reportedly associated with impairment of the mucosal antioxidative system, including a decrease in SOD activity or an increase in oxyradical production (Ogino et al, 1992;Chen et al, 1993). Free radical scavengers such as SOD and GSH attenuate the microvascular damage observed in such models and play a role in maintaining mucosal integrity by counteracting oxygen-derived free radicals (Perry et al, 1986;Loguercio et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

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Aggravation by Paroxetine, a Selective Serotonin Reuptake Inhibitor, of Antral Lesions Generated by Nonsteroidal Anti-Inflammatory Drugs in Rats

Takeuchi

Tanaka²,

Nukui³

et al. 2011

J Pharmacol Exp Ther

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Recent clinical studies have suggested a risk of adverse gastric reactions from the concomitant use of selective serotonin (5-HT) reuptake inhibitors (SSRIs) with nonsteroidal anti-inflammatory drugs (NSAIDs). We examined the adverse effects of SSRIs on antral lesions produced by indomethacin in rats. Rats fasted for 24 h were refed for 1 h, then administered indomethacin (30 mg/kg s.c.) 1 h after the refeeding and killed 6 h later. Paroxetine (1-10 mg/kg) was given orally 30 min before indomethacin. Indomethacin caused antral lesions in refed rats. Paroxetine dose-dependently aggravated these lesions, despite provoking no damage by itself. Similar results were obtained when other NSAIDs such as diclofenac, flurbiprofen, and loxoprofen were coadministered with paroxetine or when indomethacin was coadministered with other antidepressants such as fluvoxamine and milnacipran, but not imipramine or maprotiline. Exogenous 5-HT also worsened the indomethacin-induced antral damage, whereas the aggravating effect of paroxetine was attenuated by ondansetron, a selective 5-HT 3 antagonist, but not antagonists for other 5-HT receptor subtypes. Indomethacin plus paroxetine had no effect on gastric secretion but significantly decreased mucosal superoxide dismutase (SOD) activity as well as GSH content. The antral damage induced by indomethacin plus paroxetine was significantly prevented by antisecretory (acid or pepsin) agents and mucosal protective agents as well as SOD and allopurinol. These results suggest that SSRIs aggravate NSAID-induced antral lesions, probably via the activation of 5HT 3 receptors, and the mechanism of aggravation may involve the corrosive action of acid/ pepsin as well as an impaired antioxidative system.

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Section: Discussionsupporting

confidence: 51%

Section: Discussionmentioning

confidence: 99%

Aggravation by Paroxetine, a Selective Serotonin Reuptake Inhibitor, of Antral Lesions Generated by Nonsteroidal Anti-Inflammatory Drugs in Rats

Takeuchi

Tanaka²,

Nukui³

et al. 2011

J Pharmacol Exp Ther

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“…Ogino et al (11) showed that the antiulcer effect of rebamipide might be related to the inhibition of the production of reactive oxy gen species by activated neutrophils in a diethyldithio carbamate-induced antral ulcer model in rats. Recently, it was indicated that rebamipide was one of the most potent hydroxyl radical scavengers studied by electron spin resonance (12).…”

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confidence: 99%

Protective Effect of Rebamipide against Hydrogen Peroxide-Induced Hemorrhagic Mucosal Lesions in Rat Stomach

Sakurai

Yamasaki

1994

Japanese Journal of Pharmacology

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ABSTRACT-Intragastric administration of 6°1o H202 induces gastric mucosal hemorrhagic lesions in rats. Intraperitoneal administration of rebamipide at 10 to 100 mg/kg dose-dependently prevented the H202 induced mucosal lesions. The fact that cimetidine, ranitidine and omeprazole could not prevent the gastric mucosa from developing H202-induced lesions indicates that acid secretion might not be the main cause of these lesions. The protective effect of rebamipide was partially reduced by indomethacin and completely blocked by diethyl maleate, a glutathione depressor. Gastric mucosal glutathione level and glutathione peroxidase and superoxide dismutase (SOD) activities were significantly decreased by 6% H202 instillation. Rebamipide at 100 mg/kg significantly inhibited the decreases in gastric mucosal glutathione level and SOD activity. These results suggest that H202-induced gastric mucosal lesions might partially involve a decrease in defense activities against reactive oxygen species and that the protective effect of rebamipide might be related to its ability to improve oxidative stress in gastric mucosa.

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“…17 20) Rebamipide has an inhibitory eŠect on reactive oxygen species generation and is commonly used as a drug to treat gastric ulcers and acute and chronic gastritis. 21,22) According to reports, the oral administration of rebamipide is eŠective for canker sores 23) and recurrent aphthous stomatitis, which is an essential diagnostic criterion for Behcet's syndrome. 24) Furthermore, since the preventive eŠects of rebamipide on stomatitis were reported by Kawata et al, some medical institutions have used mouthwash with rebamipide as the active ingredient.…”

Section: Introductionmentioning

confidence: 99%

Effects of a Rebamipide Mouthwash on Stomatitis Caused by Cancer Chemotherapy<br/>—Evaluation of the Efficacy by Patients Themselves—

et al. 2017

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Anticancer drug-induced stomatitis develops in 30％ to 40％ of cancer cases that undergo chemotherapy. However, medications for this condition are not commercially available in Japan. Upon obtaining approval of the ethics committee, a mouthwash containing rebamipide as the active ingredient (rebamipide mouthwash) was administered to one inpatient and four outpatients, who had developed stomatitis caused by cancer chemotherapy. Starting from 14 d after the administration of the rebamipide mouthwash, the patients scored a stomatitis survey on oral state, pain level, and diet and recorded the number of times they gargled, as well as any stomatitis observations, in a stomatitis diary. The total scores for the points for each of the three types of survey sections were classiˆed into Grades 0 to 4 and evaluated as a stomatitis evaluation score (SES). The SES became``0'' in three out of theˆve patients within 14 d of treatment. No change in SES was found in one patient. In the remaining patients, SES became``0'' once but increased again later. Using image analysis software (ImageJ), the area at which the stomatitis was observed was measured. When comparing SES and change in the area in patients who agreed to participate, gradual reductions in the extent of stomatitis was observed even during the period when SES did not change. Having patientsˆll in an observation chart was eŠective for grasping changes in symptoms in outpatients.

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Antiulcer mechanism of action of rebamipide, a novel antiulcer compound, on diethyldithiocarbamate-induced antral gastric ulcers in rats

Cited by 88 publications

References 32 publications

Aggravation by Paroxetine, a Selective Serotonin Reuptake Inhibitor, of Antral Lesions Generated by Nonsteroidal Anti-Inflammatory Drugs in Rats

Aggravation by Paroxetine, a Selective Serotonin Reuptake Inhibitor, of Antral Lesions Generated by Nonsteroidal Anti-Inflammatory Drugs in Rats

Protective Effect of Rebamipide against Hydrogen Peroxide-Induced Hemorrhagic Mucosal Lesions in Rat Stomach

Effects of a Rebamipide Mouthwash on Stomatitis Caused by Cancer Chemotherapy<br/>—Evaluation of the Efficacy by Patients Themselves—

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Antiulcer mechanism of action of rebamipide, a novel antiulcer compound, on diethyldithiocarbamate-induced antral gastric ulcers in rats

Cited by 88 publications

References 32 publications

Aggravation by Paroxetine, a Selective Serotonin Reuptake Inhibitor, of Antral Lesions Generated by Nonsteroidal Anti-Inflammatory Drugs in Rats

Aggravation by Paroxetine, a Selective Serotonin Reuptake Inhibitor, of Antral Lesions Generated by Nonsteroidal Anti-Inflammatory Drugs in Rats

Protective Effect of Rebamipide against Hydrogen Peroxide-Induced Hemorrhagic Mucosal Lesions in Rat Stomach

Effects of a Rebamipide Mouthwash on Stomatitis Caused by Cancer Chemotherapy<br/>&mdash;Evaluation of the Efficacy by Patients Themselves&mdash;

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Effects of a Rebamipide Mouthwash on Stomatitis Caused by Cancer Chemotherapy<br/>—Evaluation of the Efficacy by Patients Themselves—