CDRI communication no. – 7845.
Analysing the role of COX-2 in acute oesophagitis and in melatonin-exerted protection against experimental reflux oesophagitis in rats
Article first published online: 9 OCT 2011
© 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society
Journal of Pharmacy and Pharmacology
Volume 63, Issue 12, pages 1572–1580, December 2011
How to Cite
Singh, P., Singh, N. and Palit, G. (2011), Analysing the role of COX-2 in acute oesophagitis and in melatonin-exerted protection against experimental reflux oesophagitis in rats. Journal of Pharmacy and Pharmacology, 63: 1572–1580. doi: 10.1111/j.2042-7158.2011.01358.x
- Issue published online: 8 NOV 2011
- Article first published online: 9 OCT 2011
- Received March 28, 2011Accepted October 23, 2011
- acid reflux oesophagitis;
- prostaglandin E2
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.