Gastroprotective Activity of Melatonin and Its Precursor, L-Tryptophan, against Stress-induced and Ischaemia-induced Lesions Is Mediated by Scavenge of Oxygen Radicals

Abstract

Background: Melatonin, a pineal hormone that is biosynthesized from L-tryptophan, is known to scavenge oxygen free radicals and to be present in the gut, but little is known about the role of this hormone and its precursor, L-tryptophan, in protecting the gastric mucosa from damage accompanied by increase in the generation of oxygen radicals. Methods: This study was designed to determine the effects of melatonin and L-tryptophan on the formation of acute gastric lesions induced by stress and ischaemia reperfusion and, for comparison, by topical irritants such as 100% ethanol or acidified acetylsalicylic acid. Results: It was found that pretreatment with melatonin in doses ranging from 1.2 to lOmg/kg dose-dependently reduced the stress-induced gastric lesions and was accompanied by a reduction in blood-free radicals and by attenuation of the fall in gastric blood flow. L-tryptophan applied intragastrically in doses ranging from 1 to lOOmg/kg also reduced dose-dependently the lesions induced by stress; this effect too was accompanied by a rise in gastric blood flow. Pretreatment with indomethacin, to block the biosynthesis of prostaglandins, significantly augmented the lesions produced by stress and completely abolished the protective effects of melatonin or L-tryptophan. Both melatonin and tryptophan reduced the formation of acute gastric lesions provoked by ischaemia reperfusion; this was accompanied by an increase in gastric blood flow. In contrast, melatonin and L-tryptophan failed to influence acute gastric lesions induced by topical irritants such as 100% ethanol or acidified aspirin. Conclusions: Melatonin and L-tryptophan protect the gastric mucosa from damage by stress and ischaemia reperfusion, and this action is mediated, at least in part, by the limitation in the free radicals, the stimulation of mucosal generation of PG and by the increase in gastric blood flow.