Melatonin and its precursor L-tryptophan prevent acute gastric mucosal damage induced by aspirin in humans.
Melatonin (MT) and its precursor L-tryptophan (Trp) are implicated in the protection of gastric mucosa against noxious agents. However, the role of MT and Trp on the gastric mucosal injury induced by aspirin (ASA) in human has not been investigated. Studies in animals showed that both MT and Trp given intragastrically prevents the formation of gastric mucosal lesions induced by ASA. The aim of the present study was to determine the influence of MT and Trp given orally to healthy humans on gastric mucosal lesions induced by ASA. The present study included 21 healthy, Hp-negative male volunteers with intact gastro-duodenal mucosa aging 20-50 yr. They were divided in 3 groups; group 1: 7 volunteers receiving daily 2 x 1g ASA (Polfa, Rzeszow) during 11 days; group 2: 7 healthy volunteers receiving 2x1 g ASA and MT (Lekam, Zakroczyn) (5 mg 30 min prior to ASA) during 11 days and group 3: 7 healthy volunteers receiving 2x1 g ASA and Trp (Ardeytropin, Germany) (0.5 g 30 min prior to ASA) during 11 days. Mucosal damage was evaluated at 3(rd), 7(th) and 11(th) days of ASA administration by endoscopy using Lanza score. Plasma melatonin was measured using RIA and gastric mucosal generation of PGE(2) was assessed also by RIA. ASA caused marked mucosal injury at all days of its administration except day 11(th) when only moderate lesions were evident. Pretreatment with MT or Trp alone was accompanied by a significant decrease in gastric mucosal lesion score. Gastric mucosal generation of PGE(2) was suppressed by about 90% in subjects treated with ASA without or with MT or Trp. We concluded that: MT and its precursor Trp significantly attenuate gastric mucosal lesions induced by aspirin. The action of Trp may be be mediated by MT produced in gastrointestinal tract from Trp. The gastroprotective action of MT and Trp is independent on gastric mucosal PGE2 generation.
Konturek
P C
PC
First Department of Medicine, University Erlangen-Nuremberg, Germany. Peter.Konturek@uk-erlangen.de
Celinski
K
K
Slomka
M
M
Cichoz-Lach
H
H
Burnat
G
G
Naegel
A
A
Bielanski
W
W
Konturek
J W
JW
Konturek
S J
SJ
D000208:Acute Disease; D000328:Adult; D001241:Aspirin; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D008297:Male; D008550:Melatonin / Q000097:blood / Q000494:pharmacology*; D008875:Middle Aged; D011863:Radioimmunoassay; D013276:Stomach Ulcer / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D014364:Tryptophan / Q000494:pharmacology*; D055815:Young Adult
D016166:Free Radical Scavengers; D014364:Tryptophan; D008550:Melatonin; D001241:Aspirin