THE ROLE OF MELATONIN AND L-TRYPTOPHAN IN PREVENTION OF ACUTE GASTRIC-LESIONS INDUCED BY STRESS, ETHANOL, ISCHEMIA, AND ASPIRIN

Melatonin, a pineal hormone, synthesized from L-tryptophan, is known t o exist in the gut and to scavenge oxygen free radicals but its role i n gastroprotection against acute lesions induced by various strong irr itants has been little studied. In this study, we determined the effec ts of melatonin and L-tryptophan on gastric secretion and the formatio n of acute gastric lesions induced by absolute ethanol, acidified aspi rin (ASA), stress, and ischemia-reperfusion (VR). Area of gastric lesi ons was determined by planimetry, gastric blood flow (GBF) was measure d using a H-2-gas clearance technique, and blood was withdrawn for the measurement of free radicals, plasma gastrin, and melatonin concentra tion by specific radioimmunoassay. Intragastric tig) administration of melatonin (2.5-10 mg/kg) or L-tryptophan (25-200 mg/kg) failed to aff ect gastric lesions by ethanol and ASA but dose-dependently reduced th e lesions provoked by stress and I/R; this protective effect was accom panied by a significant rise in plasma melatonin level, GBF, and DNA s ynthesis and by a marked fall in blood free radicals. L-tryptophan, wh ich significantly elevated the plasma melatonin by about 3-5-fold, als o reduced the stress and I/R-:induced lesions and blood levels of free radicals, while increasing the GEE DNA synthesis, and plasma gastrin levels. Inhibition of mucosal generation of PGE, by indomethacin aboli shed the protection and the rise of GBF afforded by melatonin and L-tr yptophan, whereas pretreatment with NG-nitro-L-arginine (L-NNA), to su ppress nitric oxide (NO) synthase, was without any effect. We conclude that melatonin applied exogenously in pharmacological doses and that released by the administration of its precursor, L-tryptophan, protect gastric mucosa from the damage induced by stress and I/R possibly by a mechanism involving the scavenging of free radicals and gastric hype remia probably mediated by endogenous prostaglandin but not NO.