11 research outputs found
Role of Cyclooxygenase-1 and -2, Phospholipase C, and Protein Kinase C in Prostaglandin-Mediated Gastroprotection
Salicylate antagonizes the effects of selective cyclooxygenase-2 inhibitors on gastric mucosal integrity in rats
Ethanol-induced mucosal damage does not increase formation of prostaglandin D2 in the rat stomach
Prostaglandin E2- and mild irritant-induced protective effects involve activation of ATP-sensitive potassium channels in the rat stomach
Effect of dexamethasone on gastric mucosal integrity in rats treated with a COX-1 or a COX-2 inhibitor
Role of cycloexygenasse-1 and cyclooxygenase-2 in ischemia-reperfusion injury in the rat small intestine
Effect of SC-560, a selective cyclooxygenase (COX)-1 inhibitor, and its modification by COX-2 inhibition in the rat stomach
Effect of proquazone and indomethacin on gastric prostaglandin synthesisin vitro andin vivo
Role of the different isoforms of cyclooxygenase and nitric oxide synthase during gastric ulcer healing in cyclooxygenase-1 and -2 knockout mice
Traditional NSAIDs, selective cyclooxygenase (COX)-2 inhibitors, and inhibitors of nitric oxide synthase (NOS) impair the healing of preexisting gastric ulcers. However, the role of COX-1 (with or without impairment of COX-2) and the interaction between COX and NOS isoforms during healing are less clear. Thus we investigated healing and regulation of COX and NOS isoforms during ulcer healing in COX-1 and COX-2 deficiency and inhibition mouse models. In this study, female wild-type COX-1(-/-) and COX-2(-/-) mice with gastric ulcers induced by cryoprobe were treated intragastrically with vehicle, selective COX-1 (SC-560), COX-2 (celecoxib, rofecoxib, and valdedoxib), and unselective COX (piroxicam) inhibitors. Ulcer healing parameters, mRNA expression, and activity of COX and NOS were quantified. Gene disruption or inhibition of COX-1 did not impair ulcer healing. In contrast, COX-2 gene disruption and COX-2 inhibitors moderately impaired wound healing. More severe healing impairment was found in dual (SC-560 + rofecoxib) and unselective (piroxicam) COX inhibition and combined COX impairment (in COX-1(-/-) mice with COX-2 inhibition and COX-2(-/-) mice with COX-1 inhibition). In the ulcerated repair tissue, COX-2 mRNA in COX-1(-/-) mice, COX-1 mRNA in COX-2(-/-) mice, and, remarkably, NOS-2 and NOS-3 mRNA in COX-impaired mice were more upregulated than in wild-type mice. This study demonstrates that COX-2 is a key mediator in gastric wound healing. In contrast, COX-1 has no significant role in healing when COX-2 is unimpaired but becomes important when COX-2 is impaired. As counterregulatory mechanisms, mRNA of COX and NOS isoforms were increased during healing in COX-impaired mice