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

Abstract

Abstract 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.