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

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 prostaglandinE(2) (dmPGE(2); a synthetic analogue of PGE(2) ; 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 PGE(2) 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, dmPGE(2) pretreatment significantly exacerbated tissue injury and simultaneously increased COX-2 expression, PGE(2) levels and MPO activity in RE-rats. Further, melatonin pretreatment significantly reduced the tissue injury, COX-2 over-expression, PGE(2) level and MPO activity in RE-rats. Melatonin offered more potent suppression of COX-2, PGE(2) 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 dmPGE(2) -induced tissue damage, COX-2 expression, PGE(2) 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.