Effect of Different Cyclooxygenase Inhibitors on Gastric Adaptive Cytoprotection Induced by 20% Ethanol

Abstract

In this study, we evaluated the effect of two different dosages of therapeutically prescribed nonsteroidal anti-inflammatory drugs (NSAIDs), ibuprofen, diclofenac, nimesulide, meloxicam, and celecoxib (ED80 for COX-1 and COX-2) on normal gastric mucosa and mucosa, previously exposed to 20% ethanol. At COX-2-inhibiting dosages, the NSAIDs tested were nonulcerogenic, and the same response profile was observed in "adapted" stomachs. Interestingly, low doses of nimesulide and celecoxib increase the levels of Prostaglandin E(2) and COX-2, and protect against subsequent 100% ethanol exposition, suggesting that these drugs may act as "mild irritants" to gastric mucosa. The ulcerogenic response to NSAIDs was prevented by the previous 20% ethanol exposition, probably the result of nitric oxide synthesis, because PGE(2) levels in gastric mucosa were reduced by these agents and a concomitant nitric oxide blockade reversed this protection.

Gastroprotective Action of Cochinchina Momordica Seed Extract Is Mediated by Activation of CGRP and Inhibition of cPLA2/5-LOX Pathway

“…However, SK-MS10 does not look to be related with PGE 2 in ethanol-induced gastric mucosa damage because a significant increase of PGE 2 was not found in the gastric tissues in spite of activation of COX-2. These results are similar to previous studies [32,33], suggesting a possibility that dominant contributor of PGE 2 level after ethanol administration might be COX-1 instead of COX-2. However, the expression of COX-1 has not been measured in the present study and further experiments are needed.…”

Pharmacological mechanisms underlying the anti-ulcer activity of methanol extract and canthin-6-one of Simaba ferruginea A. St-Hil. in animal models

“…This suggests that, the antiulcerogenic effect of both MESf and Cant are not PGE 2 modulated. This finding is similar to that of Gambero et al (2007), who observed that the ulcerogenic activity of NSAIDs can be attenuated in the stomach without the involvement of PGE 2 .…”

Effects of celecoxib in young rats: Histopathological changes in tissues and alterations of oxidative stress/antioxidant defense system

“…The pathological changes were consistent with the symptoms described for reactive gastropathy observed during treatment with NSAIDs (Rosai, 2004). Gambero et al suggested that celecoxib at low doses may act as a mild irritant in gastric mucosa due to an increased level of PGE 2 (Gambero et al, 2007). However, celecoxib at the dose used in this study may have a significant effect on COX-1 in newborns (Ozaki et al, 2002).…”