Inflammation, oxidative stress, DNA damage response and epigenetic modifications interact behind the beneficial actions of melatonin on H. pylori-mediated gastric disorders

Abstract

Helicobacter pylori (H. pylori) infection is associated with several disorders of the gastrointestinal tract, including gastric cancer. Studies of ours and others suggest that H. pylori infection may affect melatonin synthesis in the gastric epithelial cells. On the other hand, melatonin ameliorates gastric disorders as shown in clinical trials and experimental studies. Moreover, melatonin not only suppresses the DNA-damaging reaction of diet-related mutagens that can initiate carcinogenesis in gastric mucosa, but also the oxidative DNA damage evoked by reactive oxygen and nitrogen species produced during H. pylori-related gastric inflammation. H. pylori infection is associated with several functional and organic gastric disorders, including gastritis, peptic ulcer disease and gastric cancer, but the precise mechanism behind this association is not known and many pathways can be involved. Some of beneficial effects of melatonin in the gastrointestinal tract are underlined by mechanisms that likely play a role in detrimental effects of H. pylori in the stomach. Therefore, melatonin may modulate these mechanisms resulting in ameliorating H. pylori-related symptoms. In this narrative review the role of inflammation, oxidative stress, DNA damage response and epigenetic modifications in H. pylori­-associated gastric disorders will be discussed with an emphasis on gastric cancer. We also suggest that melatonin may have potential to inhibit H. pylori-mediated pathologies through its interaction with essential pathways as described herein. Overlapping mechanisms of H. pylori-associated pathogenesis and beneficial effects of melatonin justify further studies on the action of melatonin on gastric disorders associated with H. pylori infection, including clinical trials.