Protection by aspirin of indomethacin-induced small intestinal damage in rats: mediation by salicylic acid

Takeuchi, Koji; Hase, Shoko; Mizoguchi, Hideaki; Komoike, Yusaku; Tanaka, Akiko

doi:10.1016/s0928-4257(01)00009-2

Cited by 17 publications

(16 citation statements)

References 21 publications

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“…Conventional NSAIDs are known to increase gastric and intestinal motility, a phenomenon important in the gastrointestinal ulcerogenic response to these agents. However, aspirin does not increase the basal gastric motility, but even suppressed the enhanced gastric and intestine motility caused by indomethacin (14,23). It is known that gastric hypermotility may cause mucosal hypoxia and microvascular injury due to smooth muscle contraction, leading to neutrophil infiltration and release of various cytokines (24).…”

Section: Discussionmentioning

confidence: 99%

“…It is known that gastric hypermotility may cause mucosal hypoxia and microvascular injury due to smooth muscle contraction, leading to neutrophil infiltration and release of various cytokines (24). Furthermore Takeuchi et al (14) reported that salicylic acid, the metabolite of aspirin, has a cytoprotective action against NSAID-induced gastric erosion. Thus, the failure of aspirin to induce gastrointestinal damage may be explained, at least partly, by a lack of hypermotility and a protective action of salicylic acid.…”

Section: Discussionmentioning

confidence: 99%

“…Indomethacin was used to prevent further PG synthesis during the homogenization process. Samples were homogenized for 40 s at 10-s intervals and centrifuged for 10 min at 4°C at 7200´g (14). The supernatant was dried using nitrogen gas in a 37°C water bath.…”

Section: Measurement Of Bladder Pg Levelsmentioning

confidence: 99%

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Effects of NSAIDs on Bladder Function in Normal and Cystitis Rats: a Comparison Study of Aspirin, Indomethacin, and Ketoprofen

Takagi-Matsumoto

Tsukimi

et al. 2004

J Pharmacol Sci

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Abstract. To clarify the potential usefulness of non-steroidal anti-inflammatory drugs, NSAIDs, for patients with overactive bladder, we examined the effect of NSAIDs on urodynamic parameters in normal and cystitis rats and compared their ulcerogenic activity in the gastrointestinal mucosa. Cystometry was performed after administration of the conventional NSAIDs, aspirin, indomethacin, or ketoprofen. Prostaglandin levels were measured in the bladder of cystitis rats pretreated with NSAIDs. Furthermore, the ulcerogenic responses were examined. NSAIDs increased bladder capacity without any effect on micturition pressure in normal rats in the following rank order of potency: ketoprofen ³ indomethacin ³ aspirin. In cystitis rats, bladder capacity was increased and micturition frequency was decreased. The levels of prostaglandin were significantly increased in cystitis rats. All NSAIDs inhibited the increment of prostaglandin levels at doses equal to that effective in the improvement of bladder functions. When administered intraduodenally, both ketoprofen and indomethacin induced lesions in the gastrointestinal mucosa. However, aspirin had no significant effect. We demonstrate that NSAIDs are effective in animal models of disease, most likely by suppressing by prostaglandin synthesis. Since aspirin, in contrast to ketoprofen or indomethacin, did not cause any gastrointestinal lesions, aspirin might be the NSAIDs treatment of choice for overactive bladder.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Effects of NSAIDs on Bladder Function in Normal and Cystitis Rats: a Comparison Study of Aspirin, Indomethacin, and Ketoprofen

Takagi-Matsumoto

Tsukimi

et al. 2004

J Pharmacol Sci

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“…In addition, a pathway mediated by lipopolysaccharide/toll-like receptor 4 plays an important role in the development of such injuries. PG prostaglandin, HO-1 heme oxygenase-1, LPS lipopolysaccharide, TLR4 tolllike receptor 4 acid action [35]. Thus, it is impossible to cause small intestinal injuries by aspirin in experimental animals.…”

Section: Present Status Of Small Intestinal Mucosal Injury Caused By mentioning

confidence: 99%

Present status and strategy of NSAIDs-induced small bowel injury

et al. 2009

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Non-steroidal anti-inflammatory drugs (NSAIDs) are well known to cause gastroduodenal mucosal lesions as an adverse effect. Recently, the serious problem of NSAID-induced small intestinal damage has become a topic of great interest to gastroenterologists, since capsule endoscopy and balloon enteroscopy are available for the detection of small intestinal lesions. Such lesions have been of great concern in clinical settings, and their treatment and prevention must be devised as soon as possible. The prevalence of NSAIDs-induced small intestinal injury is higher than had been expected. Recent studies show that more than 50% of patients taking NSAIDs have some mucosal damage in the small intestine. The gross appearance of NSAIDinduced enteropathy varies, appearing variously as diaphragm-like strictures, ulcers, erosions, and mucosal redness. To investigate NSAID-induced enteropathy, and to rule out other specific enteropathies, other useful methods (in addition to capsule endoscopy and balloon enteroscopy) include such modalities as radiological examination of the small intestine, the permeability test, scintigraphy or the fecal excretion test using 111 Indium-labeled white blood cells, and measurement of the fecal calprotectin concentration. Diaphragm-like strictures and bleeding from mucosal breaks may be treatable with interventional enteroscopy. Misoprostol, metronidazole, and sulfasalazine are frequently used to treat NSAID-induced enteropathy, but have undesirable effects in some cases. In the experimental model, we confirmed that several existing drugs for gastroduodenal ulcers prevented indomethacin-induced small intestinal injury. Such drugs may be useful for preventing the adverse effects of NSAIDs not only in the stomach but also in the small intestine. We hope to examine these drugs in future clinical studies.

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“…Since prostanoids exhibiting a preference for EP3 and EP4 receptors stimulated the secretion of mucus and fluid and provided intestinal protection against indomethacin, it is likely that these processes contribute to the intestinal protection afforded by PGE 2 , through suppression of bacterial translocation. Interestingly, indomethacin caused a marked increase of intestinal motility, resulting in an increase in both the amplitude and frequency of contractions (12,65,70,71). Because the spasmodic nature of the intestinal motility results in a disruption of the unstirred mucus layer over the epithelium, leading to an increase in mucosal susceptibility to pathogens and irritants, the enhanced intestinal contractions may also be part of the pathogenic mechanism for indomethacin-induced small intestinal damage.…”

Section: Functional Alterations Related To Small Intestinal Protectionmentioning

confidence: 99%

Prostaglandin EP Receptors Involved in Modulating Gastrointestinal Mucosal Integrity

2010

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Abstract. Endogenous prostaglandins (PGs) play an important role in modulating the mucosal integrity and various functions of the gastrointestinal tract, and E type PGs are most effective in these actions. PGE 2 protected against acid-reflux esophagitis and prevented the development of gastric damage induced by ethanol or indomethacin, the effects mimicked by EP1 agonists and attenuated by an EP1 antagonist. Adaptive cytoprotection induced by mild irritants was also attenuated by the EP1 antagonist. On the other hand, the acid-induced duodenal damage was prevented by EP3/EP4 agonists and worsened by EP3/EP4 antagonists. Similarly, the protective effect of PGE 2 on indomethacin-induced small intestinal damage or DSS-induced colitis was mimicked by EP3/EP4 agonists or EP4 agonists, respectively. The mechanisms underlying these actions of PGE 2 are related to inhibition of stomach contraction (EP1), stimulation of duodenal HCO 3 − secretion (EP3/EP4), inhibition of small intestinal contraction (EP4), and stimulation of mucus secretion (EP3/EP4) or down-regulation of cytokine secretion in the colon (EP4), respectively. PGE 2 also showed a healing-promoting effect on gastric ulcers and intestinal lesions through the activation of EP4 receptors, the effect associated with stimulation of angiogenesis via an increase in VEGF expression. These findings should aid the development of new strategies for treatment of gastrointestinal diseases.

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Protection by aspirin of indomethacin-induced small intestinal damage in rats: mediation by salicylic acid

Cited by 17 publications

References 21 publications

Effects of NSAIDs on Bladder Function in Normal and Cystitis Rats: a Comparison Study of Aspirin, Indomethacin, and Ketoprofen

Effects of NSAIDs on Bladder Function in Normal and Cystitis Rats: a Comparison Study of Aspirin, Indomethacin, and Ketoprofen

Present status and strategy of NSAIDs-induced small bowel injury

Prostaglandin EP Receptors Involved in Modulating Gastrointestinal Mucosal Integrity

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