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.