Role of melatonin in mucosal gastroprotection against aspirin-induced gastric lesions in humans.
Melatonin and its precursor, l-tryptophan, have been shown to exert gastroprotective effects in animals, but their influence on the gastric damage by aspirin (ASA) in humans has been sparingly investigated. In this study, we designed to determine the effects of melatonin and l-tryptophan on ASA-induced gastric mucosal damage, gastric microbleeding, mucosal generation of prostaglandin E(2), and plasma melatonin, and gastrin levels. Three groups of healthy male volunteers (n = 30) with intact gastric mucosa received daily for 11 days either ASA alone or that combined with melatonin or tryptophan. Gastric blood loss and mucosal damage were evaluated at 3rd, 7th, and 11th days of ASA administration by endoscopy using Lanza score. ASA alone caused a marked rise of gastric damage and gastric blood loss, mainly at day 3rd and 7th, but they were significantly reduced at 11th day. Pretreatment with melatonin or tryptophan remarkably reduced ASA induced gastric lesions and microbleeding. Gastric mucosal generation of PGE(2) was suppressed by about 90% in all subjects treated with ASA alone without or with addition of melatonin or tryptophan. Plasma melatonin was markedly increased after treatment with melatonin or tryptophan plus ASA, but it was also raised significantly after application of ASA alone. Plasma gastrin levels were raised in subjects given melatonin or tryptophan plus ASA, but not in those with ASA alone. We conclude that melatonin and its precursor tryptophan given orally significantly reduce gastric lesions induced by ASA possibly due to (a) direct gastroprotective action of exogenous melatonin or that generated from tryptophan and (b) gastrin released from the gastric mucosa by melatonin or tryptophan.
Konturek
P C
PC
Department of Medicine, Thuringia Clinic Georgius Agricola Saalfeld, Teaching Hospital, Gemany.
Konturek
S J
SJ
Celinski
K
K
Slomka
M
M
Cichoz-Lach
H
H
Bielanski
W
W
Reiter
R J
RJ
D000328:Adult; D001241:Aspirin / Q000009:adverse effects*; D015232:Dinoprostone / Q000096:biosynthesis; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D005755:Gastrins / Q000097:blood; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D006801:Humans; D008297:Male; D008550:Melatonin / Q000097:blood / Q000494:pharmacology*; D008875:Middle Aged; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D013276:Stomach Ulcer / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D014364:Tryptophan / Q000494:pharmacology
D005755:Gastrins; D014364:Tryptophan; D008550:Melatonin; D015232:Dinoprostone; D001241:Aspirin