Cytoprotective Effects of NC-1300 and Omeprazole on HCl⋅Ethanol-Induced Gastric Lesions in Rats

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Abstract
NC-1300 (10-100 mg/kg), given p.o at 0.5, 6, 12 or 24 hr before HCl .cntdot. ethanol, dose-dependently protected the rat gastric mucosa. This protection was observed even when the gastric contents had been removed before application of HCl .cntdot. ethanol. NC-1300 (30 mg/kg), given i.p., was without effect on lesion formation in a dose which potently inhibited gastric acid secretion in pylorus-ligated rats. Pretreatment with indomethacin (5 mg/kg s.c.) resulted in no reduction in the protection by NC-1300, excluding the possible participation of endogenous prostaglandins in the protective mechanism. N-ethylmaleimide pretreatment (10 mg/kg, s.c.) slightly reduced the protective activity of NC-1300, suggesting the partial participation of endogenous sulfhydryl compounds in the NC-1300 protection. NC-1300 sulfide and mercaptobenzimidazole (compounds obtained after mixing NC-1300 with acidic solution) also dose-dependently protected against HCl .cntdot. ethanol-induced lesions when given p.o at 0.5 hr before HCl .cntdot. ethanol. The protection was significant but was considerably reduced in contrast to NC-1300 when the compounds were given 12 hr beforehand. NC-1300 sulfone had no effect on lesion formation. Omeprazole (10, 30 mg/kg), given p.o., also dose-dependently inhibited HCl .cntdot. ethanol-induced lesions. However, the duration of protection was shorter than that seen with NC-1300, i.e., the effect disappeared 12 hr later. Thus NC-1300 has a potent and long-lasting activity on HCl .cntdot. ethanol-induced gastric lesions. The mechanism by which this occurs remains unknown.