Salicylic acid blocks indomethacin- and aspirin-induced cyclo-oxygenase inhibition in rat gastric mucosa.
Salicylic acid reduces gastric mucosal lesions induced by aspirin and indomethacin. Aspirin and indomethacin reduce gastric mucosal cyclo-oxygenase activity. These studies were designed to determine whether or not salicylic acid interacts with gastric mucosal cyclo-oxygenase, decreasing the inhibitory effect of aspirin and indomethacin as has been observed in platelets and vascular tissue. The interaction between salicylic acid and two cyclo-oxygenase inhibitors, indomethacin and aspirin, was assessed on ex vivo prostaglandin generation in the rat gastric mucosa. Salicylic acid (100 mg/kg) was administered orally 30 min before the subcutaneous injection of either indomethacin (0.5-10 mg/kg) or aspirin (5.0-20 mg/kg). Pretreatment produced a shift of the mean 50% inhibitory dose for PGF2 alpha formation from 0.92 to 7.6 mg/kg for indomethacin and from 7.8 to 20 mg/kg for aspirin. Similar results were achieved with ex vivo prostacyclin synthesis as measured by the level of 6-keto-PGF 1 alpha. These data are consistent with competitive enzyme kinetics, and may, in part, explain the protective effect of salicylic acid against the ulcerogenicity of aspirin and indomethacin on the gastric mucosa.
D000818:Animals; D001241:Aspirin / Q000037:antagonists & inhibitors*; D016861:Cyclooxygenase Inhibitors; D015237:Dinoprost; D004347:Drug Interactions; D005753:Gastric Mucosa / Q000187:drug effects* / Q000201:enzymology; D007213:Indomethacin / Q000037:antagonists & inhibitors*; D008297:Male; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D011460:Prostaglandins F / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D012459:Salicylates / Q000494:pharmacology*; D020156:Salicylic Acid
D016861:Cyclooxygenase Inhibitors; D011448:Prostaglandin Antagonists; D011460:Prostaglandins F; D012459:Salicylates; D015237:Dinoprost; D020156:Salicylic Acid; D001241:Aspirin; C100006:prostaglandin F1; D007213:Indomethacin