The membrane-stabilizing action of zinc carnosine (Z-103) in stress-induced gastric ulceration in rats.
Zinc compounds have been shown to antagonize various types of gastric ulceration in rats. Zinc carnosine (Z-103), a newly developed agent was, therefore, examined for its antiulcer effect in stress-induced ulceration and also its membrane stabilizing action in rat stomachs. Cold-restraint (restrained at 4 degrees C for 2 h) stress induced severe hemorrhagic lesions together with increased mast cell degranulation and beta-glucuronidase release in the gastric glandular mucosa. Z-103 pretreatment with a single oral dose (3, 10 or 30 mg/kg) reversed these actions in a dose-dependent manner. When the compound was incubated in concentrations of 10(-7, 10(-6), 10(-5) or 10(-4) M, with isolated hepatic lysosomes, it significantly reduced the spontaneous release of beta-glucuronidase in the medium. The present study not only demonstrates the antiulcer effect of Z-103 but also indicates that the protective action is likely to be mediated by its membrane-stabilizing action on mast cells and lysosomes in the gastric glandular mucosa.
Department of Pharmacology, Faculty of Medicine, University of Hong Kong.
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Cho
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Luk
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Ogle
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002336:Carnosine / Q000031:analogs & derivatives*; D015550:Cell Degranulation / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects; D004151:Dipeptides / Q000494:pharmacology* / Q000627:therapeutic use; D005753:Gastric Mucosa / Q000187:drug effects*; D005966:Glucuronidase / Q000378:metabolism; D007425:Intracellular Membranes / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000648:ultrastructure; D008247:Lysosomes / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008407:Mast Cells / Q000187:drug effects; D009942:Organometallic Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains; D013276:Stomach Ulcer / Q000188:drug therapy* / Q000209:etiology; D013312:Stress, Physiological; D015032:Zinc; D017967:Zinc Compounds
D000897:Anti-Ulcer Agents; D004151:Dipeptides; D009942:Organometallic Compounds; D017967:Zinc Compounds; C061957:polaprezinc; D002336:Carnosine; D005966:Glucuronidase; D015032:Zinc