Effects of Zinc Acexamate (NAS-501) on Superoxide Radicals and Lipid Peroxidation of Rat Gastric Mucosa.

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 Fe[sup 2+] /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. [ABSTRACT FROM AUTHOR]