Analysing the role of COX-2 in acute oesophagitis and in melatonin-exerted protection against experimental reflux oesophagitis in rats

Objectives Cyclooxygenase(COX)‐2 is implicated in variety of pathophysiological processes, although its role in acute reflux oesophagitis is debatable. This study was designed to evaluate the role of COX‐2 during oesophagitis and in melatonin‐elicited protection in rats. Methods Reflux oesophagitis was induced in rats by ligating the pyloric end and the limiting ridge of the stomach for 5 h. Celecoxib (COX‐2 blocker; 10 mg/kg), 16,16‐dimethyl prostaglandinE₂ (dmPGE₂; a synthetic analogue of PGE₂; 10 µg/kg), melatonin (20 and 40 mg/kg) and omeprazole (10 mg/kg) were given intra‐peritoneally 45 min before induction of oesophagitis in rats. Alterations in COX‐1 and 2 gene expression and protein levels level were analysed via RT‐PCR and Western blotting, respectively. Mucosal PGE₂ level and myeloperoxidase (MPO) activity were measured using an enzyme immunoassay (EIA) kit and spectrophotometrically, respectively. Key findings COX‐2 over‐expression during reflux oesophagitis promotes inflammation of the oesophagus as celecoxib pretreatment significantly reduced tissue damage and MPO activity in rats with reflux oesophagitis (RE‐rats). By contrast, dmPGE₂ pretreatment significantly exacerbated tissue injury and simultaneously increased COX‐2 expression, PGE₂ levels and MPO activity in RE‐rats. Further, melatonin pretreatment significantly reduced the tissue injury, COX‐2 over‐expression, PGE₂ level and MPO activity in RE‐rats. Melatonin offered more potent suppression of COX‐2, PGE₂ and MPO activity than the proton‐pump inhibitor omeprazole; however, both reduced the lesion injury to a similar extent. Melatonin at a dose of 20 mg/kg failed to inhibit significantly the dmPGE₂‐induced tissue damage, COX‐2 expression, PGE₂ level and MPO activity in RE‐rats while at a higher dose of 40 mg/kg it significantly attenuated these changes. Conclusion Our results suggest that COX‐2 plays an important pro‐inflammatory role during acute reflux oesophagitis in rats and its inhibition contributes significantly to melatonin‐exerted protection against reflux oesophagitis.