Effect of Ecabet Disodium, a Novel Locally-Acting Antiulcer Drug, on Epithelial Restitution following Injury by Hypertonic NaCl in Bullfrog Stomach in vitro

Furukawa, Osamu; Kume, Eisuke; Sugamoto, Shinich; Kawauchi, Shoji; Takeuchi, Koji

doi:10.1159/000007804

Cited by 11 publications

(10 citation statements)

References 19 publications

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“…ES, a dehydroabietic acid derivative from pine resin, has been used clinically in the treatment of gastritis and gastric ulcer, and is believed to exert its effects through various mechanisms [20][21][22][23][24] . ES binds directly to the gastric mucosa, thereby protecting the mucosa against ethanol binding, and it has been shown to inhibit pepsin activity in rat and human gastric juices.…”

Section: Asaoka D Et Al Reflux Esophagitis and Upper Esophagusmentioning

confidence: 99%

Characteristic pathological findings and effects of ecabet sodium in rat reflux esophagitis

Asaoka¹,

Nagahara²,

Oguro³

et al. 2009

WJG

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AIM:To explore the pathological findings in the entire esophagus in rats with reflux esophagitis, and the effects of ecabet sodium (ES). METHODS:A rat model of chronic acid reflux esophagitis was used. In the treatment group, ES was administered after surgery (n = 16). No drug was administered postoperatively to the esophagitis group (n = 9). Shamoperated rats were used as a control group (n = 5). Rats were sacrificed on day 7 after the operation. The epithelial thickness and leukocyte infiltration were examined in the upper, middle and lower areas of the esophagus. The survival rate, incidence of esophageal ulcer, and mean surface area and number of esophageal ulcers were determined in the esophagitis and ES groups. Esophageal histology was assessed in all three groups. RESULTS:Leukocyte infiltration in the esophagitis group was 26.3 ± 22.0 in the middle esophagus and 8.2 ± 4.9 in the upper esophagus, which was significantly greater than that in the controls (1.3 ± 1.1 and 1.4 ± 1.0, respectively) (P < 0.05). The thickness of the epithelium in the esophagitis group was 210.8 ± 47.7 μm in the lower esophagus and 204.2 ± 60.1 μm in the middle esophagus, which was significantly greater than that in the controls (26.0 ± 5.5 and 21.0 ± 6.5 μm, respectively) (P < 0.05). The mean number of ulcers per animal in the ES group in the entire esophagus was 5.4 ± 2.5, which was significantly less than that in the esophagitis group (9.0 ± 3.5) (P < 0.05). The epithelial thickness in the ES group was 97.5 ± 32.2 μm in the lower esophagus, which was decreased compared with that in the esophagitis group (210.8 ± 47.7 μm) (P < 0.05). CONCLUSION:Mucosal inflammation extended to the upper esophagus close to the hypopharynx. Our study suggested that ES may have a useful defensive role in reflux esophagitis.

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Section: Asaoka D Et Al Reflux Esophagitis and Upper Esophagusmentioning

confidence: 99%

Characteristic pathological findings and effects of ecabet sodium in rat reflux esophagitis

Asaoka¹,

Nagahara²,

Oguro³

et al. 2009

WJG

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“…Ecabet is a locally acting agent with low absorption, showing a high affinity for the gastric mucus (1,2). Mechanisms of action have been reported as follows: it enhances gastric epithelial restitution, facilitates mucus synthesis and secretion, increases gastric mucosal blood flow and bicarbonate secretion, enhances gastric mucosal prostaglandin E 2 production, and inhibits gastric pepsin and pepsinogen activity (3)(4)(5). It was recently reported that ecabet enema showed a therapeutic effect in some patients with ulcerative colitis (6), but little is known about the mechanism of this effect by ecabet enema.…”

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confidence: 99%

Therapeutic Effects of Ecabet Sodium, an Antiulcer Drug, on Dextran Sodium Sulfate–Induced Ulcerative Colitis in Rats

Noto

Yamada²,

Inui³

et al. 2005

Dig Dis Sci

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Ecabet, an antiulcer drug, is reported to be effective in patients with ulcerative colitis. We investigated the effect of ecabet enema on ulcerative colitis in rats and some mechanisms underlying this effect. In vivo ecabet enema showed a therapeutic effect in the rat ulcerative colitis model induced by dextran sodium sulfate in the drinking water. The amount of ecabet bound to damaged mucosa was higher than that bound to normal mucosa 30 min after intrarectal administration. In vitro ecabet accelerated the restitution of epithelial cells, which was not affected by a TGF-beta antibody. Ecabet inhibited the leukotriene B4 production and 5-lipoxygenase activity in human neutrophils. In conclusion, ecabet enema showed a therapeutic effect in rats with ulcerative colitis. This effect may be attributable to the high binding affinity for damaged mucosa, the acceleration of restitution, and the inhibition of leukotriene B4 production.

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“…Furthermore, the decreased fluid secretion by indomethacin was significantly antagonized by the concurrent administration of NOR‐3. In addition, nitric oxide has been shown to expedite epithelial restitution in the stomach 42 , . 43 This nitric oxide‐mediated process might also reduce the bacterial invasion by repairing the injured epithelium in the small intestine.…”

Section: Discussionmentioning

confidence: 99%

Lack of small intestinal ulcerogenecity of nitric oxide‐releasing indomethacin, NCX‐530, in rats

Mizoguchi

Hase

Tanaka

et al. 2001

Aliment Pharmacol Ther

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Aim: To evaluate the intestinal ulcerogenic property of nitric oxide‐releasing indomethacin (NCX‐530) in the rat, in comparison with indomethacin. Methods: Animals were given indomethacin or NCX‐530 subcutaneously and killed 24 h later for macroscopic examination of the small intestine. Results: A single administration of indomethacin (10 mg/kg) provoked damage, mainly in the jejunum and ileum, accompanied by an increase in myeloperoxidase and inducible nitric oxide synthase activities as well as bacterial translocation. NCX‐530 at an equimolar dose (14.2 mg/kg) caused no gross damage in the small intestine, nor any significant change in inducible nitric oxide synthase and myeloperoxidase activities or bacterial translocation. NOR‐3, the nitric oxide donor (6.0 mg/kg), when administered subcutaneously together with indomethacin, significantly prevented the occurrence of intestinal lesions and other mucosal changes. Indomethacin reduced mucus and fluid secretions in the small intestine, while both NCX‐530 and NOR‐3 enhanced these secretions. NCX‐530 reduced the mucosal prostaglandin E2 contents and exhibited an anti‐inflammatory action against carrageenan‐induced paw oedema, with equal effectiveness to indomethacin. Conclusion: NCX‐530 does not cause intestinal damage, despite inhibiting cyclooxygenase activity. The reduced intestinal toxicity of NCX‐530 may be attributable to inhibition of enterobacterial translocation, partly by increasing the mucus and fluid secretions mediated by nitric oxide released from this compound.

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Effect of Ecabet Disodium, a Novel Locally-Acting Antiulcer Drug, on Epithelial Restitution following Injury by Hypertonic NaCl in Bullfrog Stomach in vitro

Cited by 11 publications

References 19 publications

Characteristic pathological findings and effects of ecabet sodium in rat reflux esophagitis

Characteristic pathological findings and effects of ecabet sodium in rat reflux esophagitis

Therapeutic Effects of Ecabet Sodium, an Antiulcer Drug, on Dextran Sodium Sulfate–Induced Ulcerative Colitis in Rats

Lack of small intestinal ulcerogenecity of nitric oxide‐releasing indomethacin, NCX‐530, in rats

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