{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T09:04:50Z","timestamp":1785488690817,"version":"3.56.0"},"reference-count":46,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,3,11]],"date-time":"2013-03-11T00:00:00Z","timestamp":1362960000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"National Scientific Center"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Pineal Research"],"published-print":{"date-parts":[[2013,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Reflux esophagitis is a common clinical entity in western countries with approximately 30% of the population experiencing the symptoms at least once every month. The imbalance between the protective and aggressive factors leads to inflammation and damage of the esophageal mucosa. We compared the effect of exogenous melatonin and melatonin derived endogenously from L\u2010tryptophan with that of pantoprazole or ranitidine in acid reflux esophagitis due to ligation of the rat pylorus and the limiting ridge between the forestomach and the corpus. Four hours after the induction of gastric reflux, an increase in mucosal lesions associated with edema of the submucosa and with the infiltration of numerous neutrophils and the fall in esophageal blood flow (<jats:styled-content style=\"fixed-case\">EBF<\/jats:styled-content>) were observed. Both melatonin and L\u2010tryptophan or pantoprazole significantly reduced the lesion index (<jats:styled-content style=\"fixed-case\">LI<\/jats:styled-content>) and raised the <jats:styled-content style=\"fixed-case\">EBF<\/jats:styled-content>. Pinealectomy that significantly decreased plasma melatonin levels aggravated LI and these effects were reduced by melatonin and L\u2010tryptophan. Luzindole, the <jats:styled-content style=\"fixed-case\">MT<\/jats:styled-content><jats:sub>2<\/jats:sub> receptor antagonist, abolished the melatonin\u2010induced reduction in LI and the rise in <jats:styled-content style=\"fixed-case\">EBF<\/jats:styled-content>. L\u2010<jats:styled-content style=\"fixed-case\">NNA<\/jats:styled-content> and capsaicin that augmented LI and decreased <jats:styled-content style=\"fixed-case\">EBF<\/jats:styled-content>, also significantly reduced melatonin\u2010induced protection and hyperemia; both were restored with L\u2010arginine and calcitonin gene\u2013related peptide (<jats:styled-content style=\"fixed-case\">CGRP<\/jats:styled-content>) added to melatonin. Upregulation of IL\u20101\u03b2 and <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u2010\u03b1 <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content>s and plasma IL\u20101\u03b2 and <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u2010\u03b1 levels were significantly attenuated by melatonin and L\u2010tryptophan. We conclude that melatonin protects against acid reflux\u2010induced damage <jats:italic>via<\/jats:italic> activation of <jats:styled-content style=\"fixed-case\">MT<\/jats:styled-content><jats:sub>2<\/jats:sub> receptors mediated by <jats:styled-content style=\"fixed-case\">NO<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">CGRP<\/jats:styled-content> released from sensory nerves and the suppression of expression and release of <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u2010\u03b1 and IL\u20101\u03b2.<\/jats:p>","DOI":"10.1111\/jpi.12048","type":"journal-article","created":{"date-parts":[[2013,3,13]],"date-time":"2013-03-13T08:15:55Z","timestamp":1363162555000},"page":"46-57","source":"Crossref","is-referenced-by-count":17,"title":["Esophagoprotection mediated by exogenous and endogenous melatonin in an experimental model of reflux esophagitis"],"prefix":"10.1111","volume":"55","author":[{"given":"Peter 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