Preventive actions of N-(3-aminopropionyl)-L-histidinato zinc (Z-103) through increases in the activities of oxygen-derived free radical scavenging enzymes in the gastric mucosa on ethanol-induced gastric mucosal damage in rats.
Z-103 at 1 to 25 mg/kg, p.o. prevented 100% ethanol-induced gastric mucosal lesions in a dose-dependent manner. Z-103 at 3 to 25 mg/kg, p.o. significantly elevated gastric mucosal superoxide dismutase (SOD)-like activity 1 hr after its administration to normal rats. In addition, Z-103 at doses (10 and 25 mg/kg, p.o.) which prevented 100% ethanol-induced gastric lesion further increased gastric mucosal SOD-like and glutathione peroxidase (GSH-px) activities elevated by 60% ethanol. Z-103 (10 and 25 mg/kg) significantly inhibited the increase in thiobarbituric acid-reactive substances in gastric mucosa injured by 60% ethanol. The combination with cycloheximide, a protein synthesis inhibitor, completely abolished the prevention of 60% ethanol-induced gastric mucosal lesions and the elevation of both free radical scavenging enzyme activities in the mucosa by Z-103 (10 mg/kg, p.o.). These results suggest that Z-103 may partly protect rat gastric mucosa against ethanol-induced damage by scavenging oxygen-derived free radicals via increases in the synthesis of SOD-like and GSH-px enzymes in the mucosa.
Ito
M
M
Department of Pharmacology, Faculty of Pharmacy, Meijo University, Nagoya, Japan.
Shii
D
D
Segami
T
T
Kojima
R
R
Suzuki
Y
Y
D000284:Administration, Oral; D000818:Animals; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002336:Carnosine / Q000031:analogs & derivatives*; D004151:Dipeptides / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000633:toxicity; D016166:Free Radical Scavengers; D005753:Gastric Mucosa / Q000187:drug effects / Q000201:enzymology*; D005979:Glutathione Peroxidase / Q000378:metabolism*; D008297:Male; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000378:metabolism*; D015032:Zinc / Q000008:administration & dosage / Q000494:pharmacology*; D017967:Zinc Compounds
D000897:Anti-Ulcer Agents; D004151:Dipeptides; D016166:Free Radical Scavengers; D009942:Organometallic Compounds; D017967:Zinc Compounds; C061957:polaprezinc; D000431:Ethanol; D002336:Carnosine; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D015032:Zinc