Pathogenic mechanism of indomethacin-induced small intestinal lesions in rats

Konaka, Akira; Yasuhiro, Tetsuya; Nishijima, S; Kato, S.; Takeuchi, K.

doi:10.1016/s0016-5085(98)80751-8

Cited by 2 publications

(6 citation statements)

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“…Data are presented as the means±SE from 5~6 rats per group. * Significant difference from the group given indomethacin alone, at P<0.05. as bacterial translocation [46,47,89,90], NCX-530 at the equimolar dose did not cause any damage with no increase of iNOS activity and bacterial translocation. NOR-3, a NO donor, when administered together with indomethacin, significantly prevented the development of intestinal lesions and other biochemical changes in the mucosa.…”

Section: Intestinementioning

confidence: 81%

“…Although depletion of endogenous PGs is a major pathogenic factor, several studies have demonstrated that NO produced by iNOS plays a key pathogenic role in the occurrence of small intestinal lesions following administration of NSAIDs [45][46][47]. A detrimental role of NO in this lesion model may be explained Fig.…”

Section: Intestinementioning

confidence: 90%

“…including bile acid, enterohepatic circulation, enterobacteria, neutrophil, TNF-a and NO, are also involved in the pathogenesis [43,[45][46][47][48]. This property is shared by nonselective COX inhibitors (except aspirin) but not COX-2 selective NSAIDs 3) .…”

Section: Effects On Ulcerogenic Responsesmentioning

confidence: 99%

“…by a cytotoxic effect of peroxynitrite produced from NO in the presence of superoxide radicals [47]. It is therefore possible that NO released from NO-NSAIDs might intensify the severity of small intestinal lesions.…”

Section: Mucosal Blood Flowmentioning

confidence: 99%

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Gastrointestinal Sparing Anti-Inflammatory Drugs - Effects on Ulcerogenic and Healing Responses

Takeuchi¹,

Tanaka²,

Suzuki³

et al. 2001

CPD

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The use of nonsteroidal antiinflammatory drugs (NSAIDs) is associated with a wide array of alterations in gastrointestinal integrity and function. Various approaches have been taken to developing NSAIDs with reduced gastrointestinal toxicity, and few have been successfully reduced the incidence of adverse reactions. These include cyclooxygenase-2 (COX-2) selective inhibitors and nitric oxide (NO)-releasing NSAIDs. Especially, much has been written about the potential of COX-2 inhibitors as anti-inflammatory and analgesic agents that lack the gastrointestinal side effects of traditional NSAIDs. COX-2 expression is most evident at sites of inflammation, while COX-1 accounts for the majority of prostaglandin synthesis in the normal gastrointestinal tract. However, there are distinct examples of circumstances in which COX-2-derived prostaglandins play a role in the maintenance of gastrointestinal mucosal integrity, particularly when the mucosa is injured, and the delineation of COX-1 and COX-2 might not be quite as clear as has been suggested. On the other hand, the rational behind the NO-releasing NSAIDs is that the NO released from the derivatives will exert beneficial effects on the gastrointestinal mucosa. This approach has been successfully demonstrated to lessen the incidence of gastrointestinal damage and to promote the healing of gastric ulcers. The present article overviews the roles of COX and NO in housekeeping functions of the gastrointestinal mucosa in various circumstances, and the effects of gastrointestinal sparing NSAIDs, mainly COX-2 selective inhibitors and NO-releasing derivatives of NSAIDs, on the ulcerogenic and healing responses in the gastrointestinal mucosa of experimental animals.

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Section: Intestinementioning

confidence: 81%

Section: Intestinementioning

confidence: 90%

Section: Effects On Ulcerogenic Responsesmentioning

confidence: 99%

Section: Mucosal Blood Flowmentioning

confidence: 99%

See 2 more Smart Citations

Gastrointestinal Sparing Anti-Inflammatory Drugs - Effects on Ulcerogenic and Healing Responses

Takeuchi¹,

Tanaka²,

Suzuki³

et al. 2001

CPD

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show abstract

“…Although the damaging effects of NSAIDs are most often ascribed to the impairment in prostaglandin synthesis and the disturbances in mucosal blood flow and superoxide radical generation [11][12][13], more recent data point to a detrimental action of these drugs on processes associated with cellular proliferation, cellcycle progression and apoptosis [10,[14][15][16]. Other recently recognized cytotoxic effects of NSAIDs are triggered by an increase in mucosal generation of proinflammatory cytokines and disturbances in the nitric oxide signalling pathway [15,[17][18][19].…”

Section: Introductionmentioning

confidence: 99%