Gastric motility is an important factor in the pathogenesis of indomethacin-induced gastric mucosal lesions in rats

Ueki, Shigeru; Takeuchi, Koji; Okabe, Susumu

doi:10.1007/bf01535735

Cited by 72 publications

(58 citation statements)

References 24 publications

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“…Takeuchi et al (8,9) reported increased amplitude of antral contractions in indomethacin-induced gastric lesions in rats and suggested that gastric hypercontractility could play an important role in the pathogenesis of this condition. However, Fioramonti and Bueno (10) showed that indomethacin-induced gastric ulceration was associated with (11) were not able to show any difference in gastric antral motility after NSAID administration in men.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have shown that NSAIDs are associated with altered gastroduodenal motility (6)(7)(8)(9)(10). Some data indicate that the administration of NSAIDs is followed by either increased gastric contractility, which correlates with gastric damage (6-9) or decreased intestinal spiking amplitude and disruption of migrating motor complexes (10), with no correlation with gastric damage.…”

Section: Introductionmentioning

confidence: 99%

“…In spite of a number of studies showing different effects of NSAIDs on antral motor activity (6)(7)(8)(9)11), the motor function of the proximal stomach and the gastric emptying of liquid meals in indomethacin-induced gastropathy have not been studied extensively. In the present study we determined whether changes in gastric tone and emptying of nutrient or non-nutrient meals correlate with mucosal lesions and neutrophil infiltration in indomethacin-induced gastric damage in rats.…”

Section: Introductionmentioning

confidence: 99%

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Decreased gastric tone and delayed gastric emptying precede neutrophil infiltration and mucosal lesion formation in indomethacin-induced gastric damage in rats

Souza

Troncon

Cunha

et al. 2003

Braz J Med Biol Res

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Gastric antral dysmotility has been implicated in the pathogenesis of indomethacin-induced gastric damage, but the relationship between gastric motor abnormalities and mucosal lesions has not been extensively studied. We investigated whether changes in gastric tone and gastric retention correlate with mucosal lesions and neutrophil migration in indomethacin-induced gastric damage in rats. Indomethacin, either 5 or 20 mg/kg , was instilled into the stomach, and then gastric damage, neutrophil migration, gastric tone and gastric retention were assessed 1 or 3 h later. Gastric damage was calculated as the sum of the lengths of all mucosal lesions, and neutrophil migration was measured by assaying myeloperoxidase activity. Gastric tone was determined by a plethysmometric method, and gastric retention of either saline or Sustacal ® was evaluated by a scintigraphic method. Gastric damage was detectable 3 h after either INDO-5 or INDO-20, but not after 1 h. Neutrophil migration was significantly higher 3 h after INDO-20 as compared with INDO-5 or control group, but not after 1 h. Values of gastric tone 1 and 3 h after either INDO-5 (1 h = 1.73 ± 0.07 ml; 3 h = 1.87 ± 0.03 ml) or (1 h = 1.70 ± 0.02 ml; 3 h = 1.79 ± 0.03 ml) were significantly lower than in controls (1 h = 1.48 ± 0.05 ml; 3 h = 1.60 ± 0.06 ml). Gastric retention of saline was higher 1 h after INDO-5 (58.9 ± 3.3%) or INDO-20 (56.1 ± 3.1%) compared to control (45.5 ± 1.7%), but not after 3 h. There were no differences concerning gastric retention of Sustacal ® between the various groups. Indomethacin induced decreased gastric tone and delayed gastric emptying, which precede mucosal lesion and neutrophil infiltration. These results indicate that there is no relationship between these gastric motor abnormalities and mucosal lesion in indomethacin-induced gastropathy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Decreased gastric tone and delayed gastric emptying precede neutrophil infiltration and mucosal lesion formation in indomethacin-induced gastric damage in rats

Souza

Troncon

Cunha

et al. 2003

Braz J Med Biol Res

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“…The length (mm) of each lesion was measured, summed per stomach and used as a lesion score. In a separate study, the stomachs were perfused with 150 mM HCl (1 ml/hr) during a 4-hr test period according to the previously published method (12). Acid perfusion was started im mediately after injection of indomethacin, the animals were killed 4 hr later, and the stom achs were treated with formalin and examined for lesions.…”

Section: Macroscopic Evaluation Of Gastric Lesionsmentioning

confidence: 99%

Effects of Sulfhydryl-Related Compounds on Indomethacin-Induced Gastric Lesions in Rats: Role of Endogenous Sulfhydryls in the Pathogenesis.

1992

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ABSTRACT-The role of mucosal sulfhydryl (SH) in the pathogenesis of indomethacin induced gastric lesions was investigated in rats. Indomethacin (25 mg/kg, s.c.) caused high-amplitude gastric contractions, resulting in linear hemorrhagic lesions in the cor pus mucosa within 4 hr, but did not induce any changes in the mucosal SH levels. These lesions were prevented significantly by prior s.c. administration of cysteamine, glutathione (GSH) or diethylmaleate (DEM), irrespective of whether the mucosal SH was increased by the former two agents or reduced by the latter. N-Ethylmaleimide (NEM) tended to worsen such lesions without any effect on the mucosal SH contents. Gastric hypermotility caused by indomethacin was inhibited significantly by DEM, cysteamine and GSH, while acid secretion was reduced by DEM and NEM. Both cysteamine and GSH prevented the indomethacin-induced linear lesions even in the stomach perfused with 150 mM HC1, whereas in the animals treated with DEM, non linear damage was induced exclusively in the antrum by indomethacin in the presence of acid. We conclude that the mucosal SH has no relation to the ulcerogenicity of in domethacin in the gastric corpus mucosa.The mechanisms of gastric protection are considered to involve at least two endogenous mediators such as prostaglandins (PGs) and sulfhydryl (SH) substances in the mucosa (1). Participation of PGs has been demonstrated in various experimental ulcer models (2-4), while the role of SH has been exclusively studied in relation to gastric cytoprotection against necrotizing agents (5-7). Since en dogenous SH substances, mainly present as in tracellular glutathione (GSH), have a variety of actions in the body (8), they might have roles in the development of other lesion mod els which have different pathogenetic mecha nisms. In fact, Konturek et al. (9) recently re ported the involvement of mucosal SH in the pathogenesis of stress ulcers. Yet, it remains undetermined whether the mucosal SH has some relation to indomethacin-induced gastric lesions.In the present study, we thus examined the effect of an ulcerogenic dose of indomethacin on the mucosal SH levels in the rat stomach, and investigated the relationship of endo genous SH to the ulcerogenicity of this agent by modulating the mucosal SH levels using SH-related compounds (cysteamine and GSH), an SH alkylator (N-ethylmaleimide) or an SH depletor (diethylmaleate).

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“…However, withdrawal from such therapy is not always practicable in patients who need analgesics and antipyretics (1). The basis of NSAIDs-induced gastric damage is thought to be multifactorial (2,3): i) suppression of mucosal prostaglandin (PG) synthesis via inhibition of cyclooxygenase, ii) decrease in the transmucosal potential difference, iii) decrease in mucosal blood flow, iv) effects on neutrophil function, v) inhibition of gastric HC03-secretion, and vi) enhancement of gastric motility. Among these, inhibition of PG synthesis probably plays a key role because PGs, particularly PGE2 and PGI2, are known to function in gastric defense by inhibiting acid secretion and by increasing mucus secretion and blood flow (4).…”

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confidence: 99%

Differential Effect of Benexate Hydrochloride Betadex on Prostaglandin Levels in Stomach and Inflammatory Site in Rats

Hori

Odaguchi

Jyoyama

et al. 1996

Japanese Journal of Pharmacology

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ABSTRACT-We compared the effects of an anti-ulcer agent, benexate hydrochloride betadex (BHB), on prostaglandin (PG) levels in gastric tissue and inflammatory exudate in untreated and indomethacintreated rats. BHB (100, 300 and 1000 mg/kg, p.o.) showed dose-dependent inhibition of gastric mucosal lesions induced by indomethacin (30 mg/kg, p.o.). Sustained decrease of PGs (PGE2 and 6-keto-PGFIa) in the gastric wall was observed from 0.5 to 6 hr after indomethacin treatment. BHB (300 and 1000 mg/kg) dose-dependently led to recovery of the indomethacin-induced decrease of gastric PGs at 1 and 6 hr after dosing. It did not antagonize the indomethacin-induced decrease of PG levels in the pleural exudate of carrageenin pleurisy nor did it affect the anti-inflammatory effects of indomethacin. BHB (100 to 1000 mg/kg) alone increased gastric PGE2 by 61% to 113%, while it decreased PGE2 levels in the pleural exudate by 9% to 71% at 6 hr after dosing. These results suggest that sustained increase of gastric PGE2 by BHB could be responsible for protection against indomethacin-induced gastric mucosal lesions and that BHB is a suitable anti-ulcer agent for NSAIDs without compromising their anti-inflammatory effects.

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Gastric motility is an important factor in the pathogenesis of indomethacin-induced gastric mucosal lesions in rats

Cited by 72 publications

References 24 publications

Decreased gastric tone and delayed gastric emptying precede neutrophil infiltration and mucosal lesion formation in indomethacin-induced gastric damage in rats

Decreased gastric tone and delayed gastric emptying precede neutrophil infiltration and mucosal lesion formation in indomethacin-induced gastric damage in rats

Effects of Sulfhydryl-Related Compounds on Indomethacin-Induced Gastric Lesions in Rats: Role of Endogenous Sulfhydryls in the Pathogenesis.

Differential Effect of Benexate Hydrochloride Betadex on Prostaglandin Levels in Stomach and Inflammatory Site in Rats

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