Reactive Oxygen Species-Induced Gastric Ulceration: Protection By Melatonin

Abstract

Gastric hyperacidity and ulceration of the stomach mucosa due to various factors are serious health problems of global concern. Although the mechanism of acid secretion from the parietal cells is now well understood, the processes involved in gastric ulceration are still not clear. Among the various causes of gastric ulceration, lesions caused by stress, alcohol consumption, Helicobacter pylori and due to use of non-steroidal anti-inflammatory drugs have been shown to be mediated largely through the generation of reactive oxygen species, especially the hydroxyl radical. A number of excellent drugs, developed over the decades, have proven useful in controlling hyperacidity and ulceration although their long-term use is reported to be associated with various side effects. Hence the investigations continue with an objective to find a compound possessing anti-secretory, anti-ulcer and antioxidant properties which will serve as a therapeutic agent to reduce gastric hyperacidity and ulcers. This article describes the role of reactive oxygen species in gastric ulceration, briefly presents a note on the currently available drugs controlling them, and focuses on the role of melatonin, a pineal secretory product, in protecting against gastric lesions. In experimental studies, melatonin has been shown to be effective in reducing mucosal breakdown and ulcer formation in a wide variety of situations. Additionally, the low toxicity of melatonin supports further investigation of this molecule as a promising gastro-protective agent. Finally, we include a commentary on how melatonin research with respect to gastric pathophysiology can move forward with a view to eventually using this indole as a therapeutic agent alone or in combination with the existing drugs to control gastric ulceration in humans in order to increase their efficacy and/or to reduce their side effects.

Gastroprotective effects of essential oil from Protium heptaphyllum on experimental gastric ulcer models in rats

“…Therefore, the main therapeutic target is the control of this secretion using antacids, H2 receptor blockers (ranitidine, famotidine) or proton pump blockers (omeprazole and lansoprazole) (Rao et al, 2004). However, nowadays, gastric ulcer therapy faces a major drawback because most of the drugs currently available in the market show limited efficacy against gastric diseases and are often associated with severe side effects (Bandyopadhyay et al, 2002;Lehne, 1998).…”

Anti-ulcer effect of extract of rhizome of Curcuma longa. L against aspirin-induced peptic ulcer in rats

“…Antioxidant potential of melatonin was found to be the reason for its anti-ulcer property by scavenging ROS. [36] Even though the present study shows significant ulceroprotective action of the extract of C. longa, its precise mechanism of action is not clear. Further studies are required to find out the actual mechanisms which leading to its antiulcer action.…”

Preliminary study on antiulcer effect of agomelatine and its potentiation with pyridoxine

“…MEL may act as a potent free radical scavenger, by neutralizing hydroxyl and peroxyl radicals among others, preventing lipid membrane peroxidation, apoptosis, and protecting the DNA from the damage induced by free radicals. 18,19 The presented study has demonstrated that pre-treatment with Agomelatine protected the gastric mucosa from ulcer induction by absolute ethanol, and the protection of the gastric mucosa was morphologically improved when the doses were increased. The repair of ulcer damage requires a complete reestablishment of the connective tissue of the mucosa, the underlying submucosa, the re-formation of glandular architecture, and the growth of new blood vessels.…”