{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T06:39:01Z","timestamp":1777531141191,"version":"3.51.4"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2011,12,1]],"date-time":"2011-12-01T00:00:00Z","timestamp":1322697600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>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 \u00b5g\/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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Key findings<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1111\/j.2042-7158.2011.01358.x","type":"journal-article","created":{"date-parts":[[2011,10,10]],"date-time":"2011-10-10T17:49:41Z","timestamp":1318268981000},"page":"1572-1580","source":"Crossref","is-referenced-by-count":10,"title":["Analysing the role of COX-2 in acute oesophagitis and in melatonin-exerted protection against experimental reflux oesophagitis in rats"],"prefix":"10.1093","volume":"63","author":[{"given":"Pratibha","family":"Singh","sequence":"first","affiliation":[{"name":"Division of Pharmacology, Central Drug Research Institute, C.S.I.R , Lucknow, Uttar Pradesh,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neetu","family":"Singh","sequence":"additional","affiliation":[{"name":"Division of Pharmacology, Central Drug Research Institute, C.S.I.R , Lucknow, Uttar Pradesh,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gautam","family":"Palit","sequence":"additional","affiliation":[{"name":"Division of Pharmacology, Central Drug Research Institute, C.S.I.R , Lucknow, Uttar Pradesh,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2011,12,1]]},"reference":[{"key":"2024103013292003400_cit1","first-page":"59","article-title":"Optimizing medical therapy for gastroesophageal reflux disease: state of the art","volume":"3","author":"Katz","year":"2003","journal-title":"Rev Gastroenterol Disord"},{"key":"2024103013292003400_cit2","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1159\/000075698","article-title":"Increased expression of cytokines and adhesion molecules in rat chronic esophagitis","volume":"68","author":"Hamaguchi","year":"2003","journal-title":"Digestion"},{"key":"2024103013292003400_cit3","doi-asserted-by":"crossref","first-page":"9049","DOI":"10.1016\/S0021-9258(18)52976-8","article-title":"Molecular cloning of human prostaglandin endoperoxide synthase type II and demonstration of expression in response to cytokines","volume":"268","author":"Jones","year":"1993","journal-title":"J Biol Chem"},{"key":"2024103013292003400_cit4","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1053\/gast.2001.29781","article-title":"Duodenal reflux induces cyclooxygenase-2 in the esophageal mucosa of rats: evidence for involvement of bile acids","volume":"121","author":"Zhang","year":"2001","journal-title":"Gastroenterology"},{"key":"2024103013292003400_cit5","first-page":"194","article-title":"Increased levels of prostaglandins and nitric oxide in esophageal mucosa of children with reflux esophagitis","volume":"26","author":"Zicari","year":"1998","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"2024103013292003400_cit6","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1023\/A:1022635127814","article-title":"Selective COX-2 inhibition is associated with decreased mucosal damage induced by acid and pepsin in rabbit esophagitis","volume":"27","author":"Lanas","year":"2003","journal-title":"Inflammation"},{"key":"2024103013292003400_cit7","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1097\/00004836-200307000-00015","article-title":"Celecoxib associated esophagitis: review of gastrointestinal side effects from cox-2 inhibitors","volume":"37","author":"Mantry","year":"2003","journal-title":"J Clin Gastroenterol"},{"key":"2024103013292003400_cit8","first-page":"409","article-title":"Cyclooxygenase-2 (COX-2) is the key event in pathophysiology of Barrett's esophagus. Lesson from experimental animal model and human subjects","volume":"61","author":"Majka","year":"2010","journal-title":"J Physiol Pharmacol"},{"key":"2024103013292003400_cit9","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1254\/jphs.10R06CR","article-title":"Prostaglandin EP receptors involved in modulating gastrointestinal mucosal integrity","volume":"114","author":"Takeuchi","year":"2010","journal-title":"J Pharmacol Sci"},{"key":"2024103013292003400_cit10","doi-asserted-by":"crossref","first-page":"2336","DOI":"10.1023\/A:1020107915919","article-title":"Gastrointestinal melatonin: localization, function, and clinical relevance","volume":"47","author":"Bubenik","year":"2002","journal-title":"Dig Dis Sci"},{"key":"2024103013292003400_cit11","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1517\/13543784.10.3.467","article-title":"The immunotherapeutic potential of melatonin","volume":"10","author":"Maestroni","year":"2001","journal-title":"Expert Opin Investig Drugs"},{"key":"2024103013292003400_cit12","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1016\/S0006-2952(98)00180-4","article-title":"Antioxidant properties of melatonin\u2013an emerging mystery","volume":"56","author":"Beyer","year":"1998","journal-title":"Biochem Pharmacol"},{"key":"2024103013292003400_cit13","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1111\/j.1600-079X.2006.00359.x","article-title":"Regression of gastroesophageal reflux disease symptoms using dietary supplementation with melatonin, vitamins and aminoacids: comparison with omeprazole","volume":"41","author":"Pereira Rde","year":"2006","journal-title":"J Pineal Res"},{"key":"2024103013292003400_cit14","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1111\/j.1600-079X.2008.00650.x","article-title":"Melatonin protects against experimental reflux esophagitis","volume":"46","author":"Lahiri","year":"2009","journal-title":"J Pineal Res"},{"key":"2024103013292003400_cit15","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/S0021-5198(19)52665-8","article-title":"Effects of sodium polyacrylate (PANa) on acute esophagitis by gastric juice in rats","volume":"32","author":"Nakamura","year":"1982","journal-title":"Jpn J Pharmacol"},{"key":"2024103013292003400_cit16","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/S0016-5085(76)80147-3","article-title":"Gastric antisecretory and antiulcer properties of PGE2, 15-methyl PGE2, and 16, 16-dimethyl PGE2. Intravenous, oral and intrajejunal administration","volume":"70","author":"Robert","year":"1976","journal-title":"Gastroenterology"},{"key":"2024103013292003400_cit17","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1136\/gut.2005.081943","article-title":"Roles of cyclooxygenase 2 and microsomal prostaglandin E synthase 1 in rat acid reflux oesophagitis","volume":"55","author":"Hayakawa","year":"2006","journal-title":"Gut"},{"key":"2024103013292003400_cit18","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1159\/000048835","article-title":"Effect of local application of growth factors on gastric ulcer healing and mucosal expression of cyclooxygenase-1 and -2","volume":"64","author":"Brzozowski","year":"2001","journal-title":"Digestion"},{"key":"2024103013292003400_cit19","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1016\/0076-6879(90)86172-R","article-title":"Assessment of leukocyte involvement during ischemia and reperfusion of intestine","volume":"186","author":"Grisham","year":"1990","journal-title":"Methods Enzymol"},{"key":"2024103013292003400_cit20","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","article-title":"A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding","volume":"72","author":"Bradford","year":"1976","journal-title":"Anal Biochem"},{"key":"2024103013292003400_cit21","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1001\/archsurg.139.7.712","article-title":"Increased acid exposure in patients with gastroesophageal reflux disease influences cyclooxygenase-2 gene expression in the squamous epithelium of the lower esophagus","volume":"139","author":"Hamoui","year":"2004","journal-title":"Arch Surg"},{"key":"2024103013292003400_cit22","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.jss.2007.01.002","article-title":"Neither antioxidants nor COX-2 inhibition protect against esophageal inflammation in an experimental model of severe reflux","volume":"142","author":"Murphy","year":"2007","journal-title":"J Surg Res"},{"key":"2024103013292003400_cit23","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/0016-5085(80)90767-2","article-title":"Radiation esophagitis in the opossum: radioprotection with indomethacin","volume":"78","author":"Northway","year":"1980","journal-title":"Gastroenterology"},{"key":"2024103013292003400_cit24","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1038\/bjc.1997.192","article-title":"Induction of cyclo-oxygenase-2 mRNA by prostaglandin E2 in human prostatic carcinoma cells","volume":"75","author":"Tjandrawinata","year":"1997","journal-title":"Br J Cancer"},{"key":"2024103013292003400_cit25","first-page":"189","article-title":"Pathology of reflux esophagitis and its complications","volume-title":"Surgery of the Oesophagus","author":"Orlando","year":"1988"},{"key":"2024103013292003400_cit26","first-page":"55","article-title":"Inflammation and repair","volume-title":"Pathologic Basis of Disease","author":"Robbins","year":"1979","edition":"2nd"},{"key":"2024103013292003400_cit27","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1016\/0016-5085(87)90256-3","article-title":"16,16-Dimethyl prostaglandin E2 aggravates gastric mucosal injury induced by histamine in rats. Possible role of the increased mucosal vascular permeability","volume":"93","author":"Takeuchi","year":"1987","journal-title":"Gastroenterology"},{"key":"2024103013292003400_cit28","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1159\/000088365","article-title":"Biphasic effect of prostaglandin E2 in a rat model of esophagitis mediated by EP1 receptors: relation to pepsin secretion","volume":"72","author":"Yamato","year":"2005","journal-title":"Digestion"},{"key":"2024103013292003400_cit29","first-page":"71","article-title":"Cytokine-induced neutrophil accumulation in the pathogenesis of acute reflux esophagitis in rats","volume":"16","author":"Yamaguchi","year":"2005","journal-title":"Int J Mol Med"},{"key":"2024103013292003400_cit30","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.jneuroim.2005.05.002","article-title":"Anti-inflammatory actions of melatonin and its metabolites, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK), in macrophages","volume":"165","author":"Mayo","year":"2005","journal-title":"J Neuroimmunol"},{"key":"2024103013292003400_cit31","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/0006-8993(87)90311-8","article-title":"Melatonin, 5-methoxytryptamine and some of their analogs as cyclo-oxygenase inhibitors in rat medial basal hypothalamus","volume":"405","author":"Franchi","year":"1987","journal-title":"Brain Res"},{"key":"2024103013292003400_cit32","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1182\/blood-2005-09-3691","article-title":"Melatonin suppresses macrophage cyclooxygenase-2 and inducible nitric oxide synthase expression by inhibiting p52 acetylation and binding","volume":"108","author":"Deng","year":"2006","journal-title":"Blood"},{"key":"2024103013292003400_cit33","first-page":"54","article-title":"Melatonin for the treatment of gastroesophageal reflux disease","volume":"14","author":"Werbach","year":"2008","journal-title":"Altern Ther Health Med"},{"key":"2024103013292003400_cit34","first-page":"361","article-title":"Protective influence of melatonin against acute esophageal lesions involves prostaglandins, nitric oxide and sensory nerves","volume":"58","author":"Konturek","year":"2007","journal-title":"J Physiol Pharmacol"},{"key":"2024103013292003400_cit35","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.lfs.2003.11.022","article-title":"Production of prostaglandinE2 via bile acid is enhanced by trypsin and acid in normal human esophageal epithelial cells","volume":"75","author":"Kawabe","year":"2004","journal-title":"Life Sci"},{"key":"2024103013292003400_cit36","doi-asserted-by":"crossref","first-page":"3989","DOI":"10.1097\/00001756-199812010-00040","article-title":"Central nervous system action of melatonin on gastric acid and pepsin secretion in pylorus-ligated rats","volume":"9","author":"Kato","year":"1998","journal-title":"Neuroreport"},{"key":"2024103013292003400_cit37","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1006\/cbir.1996.0091","article-title":"Effect of melatonin on NF-kappa-B DNA-binding activity in the rat spleen","volume":"20","author":"Chuang","year":"1996","journal-title":"Cell Biol Int"}],"container-title":["Journal of Pharmacy and Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.2042-7158.2011.01358.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jpp\/article-pdf\/63\/12\/1572\/60235354\/j.2042-7158.2011.01358.x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jpp\/article-pdf\/63\/12\/1572\/60235354\/j.2042-7158.2011.01358.x.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T18:56:16Z","timestamp":1730314576000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jpp\/article\/63\/12\/1572\/6135432"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,12,1]]},"references-count":37,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2011,12,1]]},"published-print":{"date-parts":[[2011,12,1]]}},"URL":"https:\/\/doi.org\/10.1111\/j.2042-7158.2011.01358.x","relation":{},"ISSN":["0022-3573","2042-7158"],"issn-type":[{"value":"0022-3573","type":"print"},{"value":"2042-7158","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2011,12]]},"published":{"date-parts":[[2011,12,1]]}}}