Abstract

Melatonin is a tryptophan-derived molecule with pleiotropic activities which is produced in all living organisms. This “sleep” hormone is a free radical scavenger, which activates several anti-oxidative enzymes and mechanisms. Melatonin, a highly lipophilic hormone, can reach body target cells rapidly, acting as the circadian signal to alter numerous physiological functions in the body. This indoleamine can protect the organs against a variety of damaging agents via multiple signaling. This review focused on the role played by melatonin in the mechanism of esophagoprotection, starting with its short-term protection against acute reflux esophagitis and then investigating the long-term prevention of chronic inflammation that leads to gastroesophageal reflux disease (GERD) and Barrett’s esophagus. Since both of these condition are also identified as major risk factors for esophageal carcinoma, we provide some experimental and clinical evidence that supplementation therapy with melatonin could be useful in esophageal injury by protecting various animal models and patients with GERD from erosions, Barrett’s esophagus and neoplasia. The physiological aspects of the synthesis and release of this indoleamine in the gut, including its release into portal circulation and liver uptake is examined. The beneficial influence of melatonin in preventing esophageal injury from acid-pepsin and acid-pepsin-bile exposure in animals as well as the usefulness of melatonin and its precursor, L-tryptophan in prophylactic and supplementary therapy against esophageal disorders in humans, are also discussed.

Highlights

  • Gastroesophageal reflux disease (GERD) is a multifactorial process and one of the most common diseases of the upper gastrointestinal tract (GI-tract) in humans [1,2,3]

  • Among aggressive factors of exogenous origin, cigarette smoking, alcohol and non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, naproxen, indomethacin, and ibuprofen have been identified as risk factors for the development of erosive esophagitis in humans [11,12,13,14]

  • Hyperemia evoked by the reflux of gastric juice in rat esophagus was inhibited by ablation of capsaicin-sensitive sensory nerves by neurotoxic dose of capsaicin, this latter effect being reversed in part by the treatment of capsaicin-sensory inactivated rats with exogenous calcitonin gene-related peptide (CGRP) [9,26,28]

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Summary

Introduction

Gastroesophageal reflux disease (GERD) is a multifactorial process and one of the most common diseases of the upper gastrointestinal tract (GI-tract) in humans [1,2,3]. Studies in the past have shown that the local blood flow in the esophageal mucosa plays an essential role in maintaining optimal pH in response to mucosal exposure to gastric acid contents [20,21,22]. The EBF increases in response to increased secretory activity of the esophageal mucosa and during incidental acid reflux episodes of gastric content [23,24,25].

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