Ulcerogenic potential of indomethacin in arthritic and non-arthritic rats

DiPasquale, G.; Welaj, P

doi:10.1111/j.2042-7158.1973.tb09953.x

Cited by 29 publications

(11 citation statements)

References 9 publications

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“…Furthermore, it has been reported that the patients with RA are more susceptible to NSAID-induced gastropathy than other NSAID users. This observation has been reproduced in arthritic animal models, where gastric mucosal lesions induced by NSAIDs were markedly aggravated in comparison with normal animals (3,4). However, the underlying mechanism for this phenomenon still remains unclear.…”

Section: Introductionmentioning

confidence: 64%

“…It has been reported that gastric mucosal lesions induced by conventional NSAIDs, such as indomethacin, naproxen and aspirin, were significantly aggravated in these rats when compared with normal rats (3,4). Figure 1 shows the relationship between the severity of paw edema and the ulcerogenic response to indomethacin following the injection of Freund's complete adjuvant (FCA) into the planter region of the right hindfoot.…”

Section: Alteration Of Gastric Ulcerogenic Response To Nsaidsmentioning

confidence: 99%

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Alteration of Gastric Ulcerogenic and Healing Responses in Rats With Adjuvant-Induced Arthritis

Kato

Takeuchi

2002

Japanese Journal of Pharmacology

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ABSTRACT-Gastroenteropathy is the most common among patients who use non-steroidal anti-inflammatory drugs (NSAIDs) for treatment of inflammatory disorders. It is known that rheumatoid arthritic patients are more susceptible to NSAID-induced gastropathy than other NSAID users. This article reviewed our recent studies concerning the influence of arthritic conditions on gastric ulcerogenic response to NSAID and healing response of chronic gastric ulcers in rats. Gastric lesions induced by indomethacin, one of the conventional NSAIDs, were markedly aggravated in arthritic rats. This increased ulcerogenic response in arthritic rats was attributable to nitric oxide production due to up-regulation of inducible nitric oxide synthase. In arthritic rat stomachs, cyclooxygenase (COX)-2 was also up-regulated, where COX-2 selective inhibitors such as rofecoxib or celecoxib provoked gross lesions, although they caused no damage in normal rats. In addition, the healing of chronic gastric ulcers was also delayed in arthritic rats because of less expression of various growth factors such as basic fibroblast growth factors or insulin-like growth factors. Based on these findings, it is concluded that arthritic conditions alter the mucosal ulcerogenic and healing responses in the stomach. Especially, caution should be paid on the use of COX-2 selective inhibitors in rheumatoid arthritic patients.

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Section: Introductionmentioning

confidence: 64%

Section: Alteration Of Gastric Ulcerogenic Response To Nsaidsmentioning

confidence: 99%

Alteration of Gastric Ulcerogenic and Healing Responses in Rats With Adjuvant-Induced Arthritis

Kato

Takeuchi

2002

Japanese Journal of Pharmacology

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“…Indeed, the gastric ulcerogenic response to NSAIDs, such as indomethacin, naproxen and aspirin, is aggravated in rats with adjuvant-induced arthritis as compared with normal rats [2, 3, 4, 11]. In arthritic rats Schleyerbach and Wedde [2]further demonstrated a marked aggravation of not only NSAID-induced gastric lesions but also Shay’s ulceration.…”

Section: Discussionmentioning

confidence: 99%

Delayed Healing of Gastric Ulcers in Adjuvant Arthritis Rats: Role of Acid Secretion and Basic Fibroblast Growth Factor

et al. 2001

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Background/Aim: We examined the healing process of chronic gastric ulcers in adjuvant-induced arthritic rats and investigated the mechanism for delayed ulcer healing in arthritic rats, in relation to acid secretion and basic fibroblast growth factor (bFGF). Methods: Arthritis was induced in male dark Agouti rats by a single injection of Freund’s complete adjuvant (FCA), while gastric ulcers were induced by thermal cauterization (70°C for 30 s) 7 days after FCA injection. Results: Injection of FCA induced severe arthritis in all animals with a marked acid hypersecretion. The healing of gastric ulcers was significantly delayed in arthritic rats as compared with normal rats. Daily administration of indomethacin delayed ulcer healing in both normal and arthritic rats, but this effect was more pronounced in the latter. In contrast, the healing of gastric ulcers was significantly promoted in both normal and arthritic rats by omeprazole at a dose that inhibited acid secretion completely. The delayed healing of gastric ulcers was not influenced by twice daily administration of N^G-nitro-L-arginine methyl ester, aminoguanidine or FR167653 (IL-1/TNF-α synthesis inhibitor), but was significantly accelerated by CS-23 (recombinant human bFGF) in a dose-dependent manner, without effect on the acid secretion. The expression of bFGF was markedly increased after ulceration, but this response was decreased in arthritic rats. Conclusion: The healing of gastric ulcers was delayed in arthritic rats, and this mechanism may be partly attributable to both acid hypersecretion and less expression of bFGF.

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“…The Mycobacterial component is 1) Inoculating adjuvants in susceptible rat strains engenders other pathologies, besides the arthropathy, which may profoundly affect drug action in vivo e.g. hypoalbuminemia, lesions in drug metabolism [8][9][10], altered drug sensitivity [8,9,11,12], tissue and cell fragility [13,14] and anemia (15).…”

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confidence: 99%

Standardisation of arthritogenic adjuvants for evaluating anti-inflammatory and immunosuppressant drugs

Whitehouse

Beck

1974

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Ulcerogenic potential of indomethacin in arthritic and non-arthritic rats

Cited by 29 publications

References 9 publications

Alteration of Gastric Ulcerogenic and Healing Responses in Rats With Adjuvant-Induced Arthritis

Alteration of Gastric Ulcerogenic and Healing Responses in Rats With Adjuvant-Induced Arthritis

Delayed Healing of Gastric Ulcers in Adjuvant Arthritis Rats: Role of Acid Secretion and Basic Fibroblast Growth Factor

Standardisation of arthritogenic adjuvants for evaluating anti-inflammatory and immunosuppressant drugs

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