Melatonin is a potent reactive
oxygen metabolite scavenger and
antioxidant that has been shown to influence many physiological functions of the gastrointestinal (GI) tract including secretion, motility, digestion and absorption of nutrients. The role of
melatonin in gastroduodenal defense and
ulcer healing has been the subject of recent investigations.
Melatonin produced in the GI mucosa plays an important role in protection against noxious agents thus contributing to the maintenance of GI integrity and to esophageal protection, gastroprotection and
ulcer healing. This review was designed to summarize the involvement of
melatonin, conventionally considered as a major
hormone of the pineal gland, in the maintenance of gastric mucosal integrity, gastroprotection,
ulcer healing and intestinal disorders.
Melatonin was originally shown to attenuate gastric mucosal lesions but controversy exists in the literature as to whether
melatonin derived from the pineal gland, considered as the major source of this
indole, or rather gastrointestinal
melatonin plays predominant role in gastroprotection. Intragastric and central administration of exogenous
melatonin and
L-tryptophan, this indoleamine precursor, affords protection against gastric hemorrhagic damage caused by the exposure of gastric mucosa to variety of non-topical and topical ulcerogens such as stress,
ethanol and
ischemia-reperfusion. The speed of
ulcer healing in experimental animals and humans is accelerated by
melatonin. This indoleamine could be also effective against the esophageal lesions provoked by
reflux esophagitis in animal models and prevents the incidence of
GERD in humans. The
melatonin-induced gastroprotection is accompanied by an increase in gastric blood flow, plasma
melatonin concentration, enhancement in mucosal generation of
PGE2,
luminal NO content and plasma
gastrin levels.
Melatonin scavenges reactive
oxygen metabolites, exerts anti-oxidizing and anti-inflammatory actions and inhibits the formation of
metalloproteinases- 3 and -9; both implicated in the pathogenesis of gastrointestinal injury and formation of
gastric ulcers. Blockade of MT2 receptors by
luzindole, significantly attenuated
melatonin- and
L-tryptophan-induced protection and increased the speed of
ulcer healing and these effects were accompanied by an increase in the GBF and
luminal content of NO suggesting that
melatonin exhibits gastroprotection and
hyperemia via activation of MT2 receptors and release of NO. The accumulated evidence indicates that the
melatonin-induced gastroprotection and the enhancement in healing rate of
gastric ulcers may involve the gastroprotective factors derived from the activation of PG/COX and NO/NOS systems as well as
gastrin which also was shown to exhibit protective and trophic effects in the upper GItract. Interestingly,
pinealectomy, which suppressed plasma
melatonin levels, markedly exacerbated gastric lesions induced by topical and non-topical ulcerogens and these effects are counteracted by a concurrent supplementation with
melatonin. Evidence is provided that exogenous
melatonin and that converted from its precursor,
L-tryptophan, attenuates acute gastric lesions and accelerates
ulcer healing via interaction with MT2 receptors due to an enhancement of gastric microcirculation, probably mediated by NO and PG derived from NOS and COX-1 and COX-2 overexpression and activity. The pineal gland plays an important role in the limitation of gastric mucosal injury and the acceleration of
ulcer healing via releasing endogenous
melatonin, which attenuates oxidative stress and exerts anti-inflammatory action.