Cyclo-oxygenase-2 expression and prostaglandin E2 production in experimental chronic gastric ulcer healing.
Prostaglandin, a key molecule that stimulates the complex array of ulcer healing mechanism, gets synthesized in the mucosal cells by cyclooxygenase (COX) enzymes: COX-1 and COX-2. High expression level of COX-2 protein at healing ulcer margins highlights its role in ulcer healing and hypothesized to be an important contributing factor in healing mechanism of anti-ulcer drugs. In the present study we have compared the expression profile of COX-2 protein, prostaglandin E2 (PGE2) levels and myeloperoxidase activity in acetic acid induced chronic gastric ulcer model in rats treated with omeprazole, misoprostol and COX-2 selective nonsteroidal anti-inflammatory drug (NSAID) celecoxib. Both COX-2 expression and PGE2 level have shown differential pattern in different treated groups parallel to the differential effects of these drugs on ulcer healing. Omeprazole has significantly elevated the expression level of COX-2 protein, PGE2 level (19.37%), and decreased myeloperoxidase activity (81.92%), thereby causing the most effective ulcer healing (89.74%). Similar trend was observed with misoprostol, but with relatively less pronounced ulcer healing and COX-2 expression. Celecoxib has retarded COX-2 expression and delayed ulcer healing. Therefore, induction of COX-2 expression leading to higher level of prostaglandin appears to be an important contributing factor in drug mediated ulcer healing apart from the respective mechanisms of different drugs.
Poonam
Dharmani
D
Division of Pharmacology, Central Drug Research Institute, Lucknow-226001, P.B. No. 173, U.P, India.
Vinay
Chauhan Singh
CS
Gautam
Palit
P
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology / Q000627:therapeutic use; D015153:Blotting, Western; D000068579:Celecoxib; D002908:Chronic Disease; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis*; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D016595:Misoprostol / Q000494:pharmacology / Q000627:therapeutic use; D009853:Omeprazole / Q000494:pharmacology / Q000627:therapeutic use; D009195:Peroxidase / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D011720:Pyrazoles / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology*
D000897:Anti-Ulcer Agents; D011720:Pyrazoles; D013449:Sulfonamides; D016595:Misoprostol; D009195:Peroxidase; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D000068579:Celecoxib; D015232:Dinoprostone; D009853:Omeprazole