Melatonin independent protective role of l-tryptophan in experimental reflux esophagitis in rats.

Melatonin is implicated in sustaining the esophageal integrity in gastro-esophageal reflux disease. However, the role of its synthetic precursor l-tryptophan is not clear in this pathology. The present study was designed to explore the effects of l-tryptophan on esophageal damage following reflux esophagitis (RE)-establishment and concurrent alterations in factors possibly influencing esophageal integrity such as esophageal melatonin level, luminal acidity, H(+)K(+)-ATPase activity, mucin and gastric PGE(2) levels. RE was established in rats by simultaneous ligation of pylorus region and fore-stomach. RE significantly decreased the esophageal-melatonin level and the expression of its synthesizing enzymes: arylalkylamine-N-acetyltransferase (AA-NAT) and hydroxyindole-O-methyltransferase (HIOMT). Administration of l-tryptophan significantly decreased the RE-induced esophageal mucosal damage, without altering the levels of melatonin. l-Tryptophan pretreatment also normalized the esophageal mucosal damage caused by melatonin receptor antagonist-luzindole. Simultaneously, l-tryptophan significantly increased the RE-decreased expression of AA-NAT with insignificant effect on HIOMT gene expression. In contrast, l-tryptophan per se caused a significant elevation in the esophageal melatonin level, with no significant effect on the expression of AA-NAT and HIOMT enzymes. Further, l-tryptophan significantly normalized the RE-induced changes in the gastric juice volume, acidity and pH. However, it did not significantly inhibit the H(+)K(+)-ATPase activity in vitro. Also, l-tryptophan significantly increased the RE-reduced mucin level, COX-2 activity and thereby PGE(2) levels. Interestingly, indomethacin (PGE(2) synthesis blocker), aggravated the RE-induced tissue injury with simultaneous changes in the gastric volume, acidity, pH and mucin content, which l-tryptophan failed to reverse, suggesting that the attenuating effect of l-tryptophan on gastric secretions could be PGE(2) driven. Thus the current study provide evidences that protective functions of l-tryptophan against RE is independent of its conversion into melatonin, and possibly involve mobilization of factors such as COX-2 derived PGE(2) and mucin that counterbalance the detrimental effect of gastric acid on esophageal mucosa, signifying the therapeutic efficacy of l-tryptophan against the esophageal pathologies.