Role of inhibition of gastric mucous secretion in the phenomenon of gastric mucosal injury by indomethacin

Menguy, René; Desbaillets, L.

doi:10.1007/bf02236444

Cited by 88 publications

(27 citation statements)

References 7 publications

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“…Therefore, we presumed that KB-5492 also inhibits aspirin-induced mucosal lesions by retaining gastric mucus. Besides being a factor in aspirin-induced lesions, it has been reported that the reduction of gastric mucus is a possible cause of the lesion formation in duced by water-immersion stress (23), in domethacin (24) and ethanol (25). In addition, it has been suggested that the healing of acetic acid-induced ulcers is closely related to the amount of mucus in the gastric mucosa (26,27).…”

Section: Discussionmentioning

confidence: 99%

Effects of the New Anti-Ulcer Agent KB-5492 on Experimental Gastric Mucosal Lesions and Gastric Mucosal Defensive Factors, as Compared to Those of Teprenone and Cimetidine.

Morimoto¹,

Shimohara²,

Oshima³

et al. 1991

Jpn.J.Pharmacol

176

115

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ABSTRACT-Effectsof KB-5492, a new anti-ulcer agent, on various experimental gastric mucosal lesions and mucosal defensive factors in rats were compared with those of teprenone and cimetidine. KB-5492 administered orally at 12.5 200 mg/kg inhibited water-immersion stress and indomethacin-induced gastric mucosal lesions in a dose-dependent manner with ED50 values of 46 and 27 mg/kg, respectively, indicat ing that KB-5492 was more potent than teprenone but less potent than cimetidine. KB-5492, administered orally at 12.5 -100 mg/kg, also inhibited ethanol-induced gas tric mucosal lesions in a dose-dependent manner with an ED50 of 23 mg/kg, so KB 5492 was 3 times more potent than teprenone, whereas cimetidine produced no ob vious inhibition. In addition, KB-5492, administered orally at 25 and 50 mg/kg twice daily for 10 consecutive days, significantly accelerated the healing of acetic acid-in duced gastric ulcers more potently than teprenone and cimetidine. KB-5492 at anti ulcer doses significantly increased gastric mucosal blood flow in normal anesthetized rats and inhibited the reduction of gastric mucosal hexosamine content induced by aspirin, but did not affect gastric acid secretion in pylorus-ligated rats. These results indicate that KB-5492 has potent and broad anti-ulcer properties, which are probably exerted by its enhancement of gastric mucosal defensive factors through increasing gastric mucosal blood flow and/or retaining gastric mucus, and not by its inhibition of gastric acid secretion.It is generally accepted that peptic ulcers are caused by a disruption in the balance of aggressive factors (gastric acid and pepsin) and mucosal defensive factors (blood flow, mucus, HC03 secretion, etc.) (1). Anti-ulcer agents have therefore been used either for suppres sing aggressive factors or for enhancing mucosal defensive factors. However, in recent years, it has been considered that different anti-ulcer agents should be used for gastric and duodenal ulcers, because of the patho physiological differences between the two ulcer types. That is, as gastric acid secretion is generally greater in duodenal ulcer patients than in normal subjects (2-4), agents such as H2-receptor antagonists or proton pump in hibitors, which strongly inhibit gastric acid secretion, show prominent effects on duodenal ulcers. In contrast, since gastric acid secretion is usually normal or below normal in gastric ulcer patients, gastric ulcers are presumed to be caused by weaknesses in gastric mucosal re sistance (4, 5). Therefore, agents which en hance mucosal defensive factors would be ex pected to show desirable effects against gastric ulcers. Although various agents in this catego ry have already been developed so far, they have not been particularly effective, so anti secretory agents are used preferably, even in the treatment of gastric ulcers.Seeking a novel agent which would enhance mucosal defensive factors more potently than existing agents, we developed 4-methoxy phenyl 4-(3,4,5-trimethoxybenzyl)-1-piperazine acetate monofumarate m...

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Section: Discussionmentioning

confidence: 99%

Effects of the New Anti-Ulcer Agent KB-5492 on Experimental Gastric Mucosal Lesions and Gastric Mucosal Defensive Factors, as Compared to Those of Teprenone and Cimetidine.

Morimoto¹,

Shimohara²,

Oshima³

et al. 1991

Jpn.J.Pharmacol

176

115

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“…at 5 mg/kg to pigs induced damage of gastric mucosal capillaries within 10 to 15 min and suggested that this capillary damage develops to severe damage to sur rounding tissues. In addition, indomethacin is reportedly known to reduce gastric mucosal blood flow (22,23), mucus secretion (24) and bicarbonate secretion (25).…”

Section: Discussionmentioning

confidence: 99%

16,16-Dimethyl prostaglandin E2 protects gastric mucosal surface epithelial cells from indomethacin-induced damage in rats.

et al. 1987

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Abstract-The protective effect of 16,16-dimethyl prostaglandin E2 (dmPGE2) against early damage induced by indomethacin in the rat gastric mucosal surface epithelial cells was studied using a scanning electron microscope. Indomethacin (10 or 25 mg/kg, p.o.) induced a widespread exfoliation of the surface epithelial cells and an exposure of the lamina propria both in the corpus and antrum within 1 hr after the administration.Pretreatment with dmPGE2 (0.3, 3 or 30 acg/kg , p.o.) 30 min before indomethacin (25 mg/kg) dose-dependently inhibited these damages.The effects of dmPGE2, at least on the surface epithelial cells in the corpus, appear to be related to the prevention of damage formation itself and is unrelated to the enhancement of reconstitution of once damaged mucosa. Enhanced gastric motility by indomethacin was potently inhibited by pretreatment with 3 and 30 ug/kg of dmPGE2, but not with 0.3 ug/kg. dmPGE2 pretreatment (30 /cg/kg) significantly decreased the absorption of indomethacin (25 mg/kg) when determined 10 min after giving indomethacin, but did not affect it when determined 30 and 60 min later. We conclude that dmPGE2 protects gastric mucosal surface epithelial cells from indomethacin injury at an early stage, partly by inhibiting gastric motility.

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“…The view is supported by the fact that prostaglandins normally serve a protective function in stomach by maintaining gastric microcirculation 35,36 and causes gastric secretion of biocarbonate 37 and mucus 38 . The test substances inhibited the indomethacin induced ulceration in rats.…”

Section: Histopathologymentioning

confidence: 99%

Untitled

2017

IJPSR

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ABSTRACT:This investigation was aimed to study the effect of few selected antioxidants, Vitamins and minerals for prevention of gastric erosion in indomethacin induced gastric mucosal damage in rats. Male Wistar rats, weighing between 200 -250 g were divided into 9 groups of 6 animals each (n = 6). The groups were treated respectively as follows Group I normal control and Group II disease control received normal saline, Group III was treated with standard drug Omeprazole, Group IV to IX received test substances for 7 days. Ulceration was induced by a single oral administration of indomethacin (30 mg/kg). Various parameters like, the volume, pH of gastric juice, total acidity, ulcer index, percentage protection, mucin content, pepsin activity and antioxidant enzymes were estimated. Histopathology of stomach epithelium was observed. The ulcer index and total acidity were significantly reduced (p < 0.05). Increase in pH was observed in ulcer induced rats pre-treated with test substances. Mucin content was found to be restored significantly in all rats pretreated with test substances, and pepsin activity was decreased significantly (p < 0.05) when compared with disease control treated rats. The alteration observed in the level of super oxide dismutase, catalase, reduced glutathione were increased in test substances treated rats and showed significant restoration. The level of myeloperoxidase and malondialdehyde were decreased significantly (p < 0.05). Histopathology of gastric mucosa confirmed the gastro-protection by test substances. The study reveals antiulcerogenic effects were observed in all test groups antioxidants, Vitamins and minerals probably by its free radical scavenging activity, antisecretory activity, cytoprotection and mucin preventing nature.

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Role of inhibition of gastric mucous secretion in the phenomenon of gastric mucosal injury by indomethacin

Cited by 88 publications

References 7 publications

Effects of the New Anti-Ulcer Agent KB-5492 on Experimental Gastric Mucosal Lesions and Gastric Mucosal Defensive Factors, as Compared to Those of Teprenone and Cimetidine.

Effects of the New Anti-Ulcer Agent KB-5492 on Experimental Gastric Mucosal Lesions and Gastric Mucosal Defensive Factors, as Compared to Those of Teprenone and Cimetidine.

16,16-Dimethyl prostaglandin E2 protects gastric mucosal surface epithelial cells from indomethacin-induced damage in rats.

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