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Effects of zinc acexamate (NAS-501) on superoxide radicals and lipid peroxidation of rat gastric mucosa.

Abstract
Zinc acexamate (NAS-501), an anti-ulcer agent, has been reported to prevent various acute experimental gastric mucosal lesions and duodenal ulcers in rats. In order to clarify the mechanisms by which NAS-501 exhibits the anti-ulcer effects, we investigated the anti-oxidative effects of NAS-501 in vitro and in vivo. NAS-501 significantly reduced the superoxide radical-dependent chemiluminescence, generated by hypoxanthine-xanthine oxidase, rat neutrophils and guinea-pig macrophages in vitro. These in vitro effects were also confirmed by electron spin resonance using a 5, 5-dimethyl-1-pyrroline-N-oxide spin-trapping method. In addition, NAS-501 significantly inhibited lipid peroxidation induced by increasing concentrations of Fe2+/ascorbate in rat gastric mucosal homogenate in vitro. Oral administration of NAS-501 (30 mg/kg) significantly inhibited production of thiobarbituric acid-reactive substance in rat gastric mucosa following per os instillation of 60% ethanol in 150 mmol/l HCl in vivo. These results suggest that NAS-501 exhibits the preventive effect from acute gastric mucosal lesions by the anti-oxidative activity.
AuthorsY Tsutsui, Y Nakamura, S Yamaguchi, N Kawanaka, M Sato
JournalPharmacology (Pharmacology) Vol. 58 Issue 4 Pg. 209-19 (Apr 1999) ISSN: 0031-7012 [Print] Switzerland
PMID10077740 (Publication Type: Journal Article)
Chemical References
  • Aminocaproates
  • Anti-Ulcer Agents
  • Antioxidants
  • Pyrazines
  • Thiobarbituric Acid Reactive Substances
  • 2-methyl-6-phenyl-3,7-dihydroimidazo(1,2-a)pyrazin-3-one
  • Superoxides
  • Hypoxanthine
  • 6-acetylaminocaproic acid
  • Xanthine Oxidase
  • Aminocaproic Acid
Topics
  • Aminocaproates
  • Aminocaproic Acid (pharmacology)
  • Animals
  • Anti-Ulcer Agents (pharmacology)
  • Antioxidants (pharmacology)
  • Electron Spin Resonance Spectroscopy
  • Gastric Mucosa (drug effects, metabolism, pathology)
  • Guinea Pigs
  • Hypoxanthine (metabolism)
  • Lipid Peroxidation (drug effects)
  • Luminescent Measurements
  • Macrophages (cytology, drug effects, metabolism)
  • Male
  • Neutrophils (cytology, drug effects, metabolism)
  • Pyrazines
  • Rats
  • Rats, Sprague-Dawley
  • Superoxides (metabolism)
  • Thiobarbituric Acid Reactive Substances (metabolism)
  • Xanthine Oxidase (metabolism)

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