Effect of indomethacin or aspirin in association with diflunisal or sodium salicylate on prostacyclin release by rat gastric mucosa.

Non-steroidal anti-inflammatory drugs (NSAIDs) have a damaging effect on gastric and intestinal mucosa due to their inhibitory action of prostaglandin (PG) synthesis by blocking cyclooxygenase activity. Prostacyclin (PGI) is the main metabolite of arachidonic acid in gastric mucosa and its production is inhibited by NSAIDs. Indomethacin or aspirin administration produce erosions and ulcers by inhibiting PGI generation in the stomach. Other NSAIDs such as diflunisal, and even more sodium salicylate in rats, produce a lower degree of gastric ulcerogenity than that observed when indomethacin or aspirin were given alone. In the present work tests were carried out to confirm if combinations of indomethacin or aspirin with diflunisal or sodium salicylate block PGI release from gastric mucosa less than the administration of the compounds alone. PGI generation by gastric mucosa was determined on aliquots of incubated mucosal strips tested for ADP-induced aggregation of human platelet rich plasma (PRP). The results were compared with those obtained with known amounts of authentic PGI on ADP-induced aggregation of PRP. The obtained data indicate that the PGI production found in rats treated with indomethacin or aspirin combined with diflunisal or sodium salicylate was higher than that found in rats treated with indomethacin or aspirin alone. This effect may be explained by competition between salicylates and other NSAIDs for binding sites on PG-synthetase and plasma proteins. [ABSTRACT FROM AUTHOR]