BACKGROUND: Cyclo-oxygenase-1 (COX-1) is believed to produce prostaglandins vital to mucosal defence, whereas cyclo-oxygenase-2 (COX-2) is induced at sites of inflammation. Little is known about the regulation of COX-2 in the stomach, particularly during the period following mucosal injury. In this study, we examined COX-1 and COX-2 expression shortly after administration of NSAIDs or ethanol. METHODS: Fasted rats were given aspirin, salicylate, indomethacin or ethanol (20% or 40%) orally. Three hours later the stomach was excised, the severity of damage scored and samples taken for RT-PCR of COX-1 and COX-2 mRNA and immunohistochemistry. Nitric oxide synthase mRNA (iNOS and eNOS) and activity were also measured. RESULTS: Aspirin, indomethacin and the higher concentration of ethanol produced widespread mucosal damage, whereas salicylate and 20% ethanol caused only superficial epithelial damage. Aspirin caused a significant increase in COX-2 mRNA expression and a marked increase in COX-2 immunoreactivity, particularly in the superficial mucosa. Expression of COX-1 (mRNA and protein) was unaffected by aspirin, as were NOS mRNA expression and enzyme activity. Pre-treatment with prostaglandin E2 prevented the induction of COX-2 by aspirin. Salicylate and indomethacin caused modest increases in COX-2 immunoreactivity but no change in COX-2 mRNA. Neither concentration of ethanol affected COX-2 mRNA or protein expression, suggesting that this was a specific response to the aspirin, rather than to injury. CONCLUSIONS: These results demonstrate a rapid up-regulation of COX-2 expression in response to aspirin, possibly representing a compensatory response to inhibition of gastric prostaglandin synthesis.
BACKGROUND:Cyclo-oxygenase-1 (COX-1) is believed to produce prostaglandins vital to mucosal defence, whereas cyclo-oxygenase-2 (COX-2) is induced at sites of inflammation. Little is known about the regulation of COX-2 in the stomach, particularly during the period following mucosal injury. In this study, we examined COX-1 and COX-2 expression shortly after administration of NSAIDs or ethanol. METHODS: Fasted rats were given aspirin, salicylate, indomethacin or ethanol (20% or 40%) orally. Three hours later the stomach was excised, the severity of damage scored and samples taken for RT-PCR of COX-1 and COX-2 mRNA and immunohistochemistry. Nitric oxide synthase mRNA (iNOS and eNOS) and activity were also measured. RESULTS:Aspirin, indomethacin and the higher concentration of ethanol produced widespread mucosal damage, whereas salicylate and 20% ethanol caused only superficial epithelial damage. Aspirin caused a significant increase in COX-2 mRNA expression and a marked increase in COX-2 immunoreactivity, particularly in the superficial mucosa. Expression of COX-1 (mRNA and protein) was unaffected by aspirin, as were NOS mRNA expression and enzyme activity. Pre-treatment with prostaglandin E2 prevented the induction of COX-2 by aspirin. Salicylate and indomethacin caused modest increases in COX-2 immunoreactivity but no change in COX-2 mRNA. Neither concentration of ethanol affected COX-2 mRNA or protein expression, suggesting that this was a specific response to the aspirin, rather than to injury. CONCLUSIONS: These results demonstrate a rapid up-regulation of COX-2 expression in response to aspirin, possibly representing a compensatory response to inhibition of gastric prostaglandin synthesis.
Authors: Xinzhi Li; Liudmila L Mazaleuskaya; Chong Yuan; Laurel L Ballantyne; Hu Meng; William L Smith; Garret A FitzGerald; Colin D Funk Journal: J Lipid Res Date: 2017-11-27 Impact factor: 5.922
Authors: Maria Eduarda Azambuja Amaral; Laura Roesler Nery; Carlos Eduardo Leite; Walter Filgueira de Azevedo Junior; Maria Martha Campos Journal: Invest New Drugs Date: 2018-02-02 Impact factor: 3.850