title: Analysing the role of COX-2 in acute oesophagitis and in melatonin-exerted protection against experimental reflux oesophagitis in rats.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Division of Pharmacology, Central Drug Research Institute, CSIR, Lucknow, Uttar Pradesh, India.
authors: Pratibha
authors: P
authors: Singh
authors: Neetu
authors: N
authors: Singh
authors: Gautam
authors: G
authors: Palit
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D015153:Blotting, Western; D051545:Cyclooxygenase 1 / Q000096:biosynthesis / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000378:metabolism*; D015232:Dinoprostone / Q000096:biosynthesis; D004789:Enzyme Activation / Q000187:drug effects; D004941:Esophagitis / Q000201:enzymology*; D004947:Esophagus / Q000473:pathology; D005764:Gastroesophageal Reflux / Q000201:enzymology* / Q000517:prevention & control*; D006471:Gastrointestinal Hemorrhage / Q000201:enzymology / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics / Q000502:physiology; D007124:Immunoenzyme Techniques; D008550:Melatonin / Q000627:therapeutic use*; D009092:Mucous Membrane / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism; D016133:Polymerase Chain Reaction; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000975:Antioxidants; D009195:Peroxidase; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D008550:Melatonin; D015232:Dinoprostone