Dose-Dependent Effects of Verapamil on Ethanol-Induced Gastric Lesions in Rats

The effects of graded doses of verapamil on ethanol-induced stomach mucosal damage were studied in rats. Gastric lesions were induced in vivo by oral administration of 80% ethanol and evaluated with regard to ulcer index, gastric mucus content, free and total acidity, lipid peroxidation and nonprotein sulfhydryl groups. Orally administered ethanol markedly increased the ulcer index and lipid peroxidation. Pretreatment of rats with verapamil (1, 5, and 25 mg/kg i.p.) was carried out 1 h before the administration of ethanol. Verapamil showed a protective effect against ethanol-induced mucosal damage only at high dose (25 mg/kg). Verapamil dose dependently decreased the total acidity, lipid peroxidation, and nonprotein sulfhydryl content. Verapamil 25 mg/kg also increased significantly the gastric mucus secretion. L-arginine (100 mg/kg) or L-nitroarginine (100 mg/kg) with verapamil were also administered to the animals to determine the role of nitric oxide in the mechanism of the gastroprotective activity of verapamil (25 mg/kg). The results indicate that reduced acidity and lipid peroxidation and increased mucus secretion participate in the protective effects of verapamil against ethanol damage. On the other hand, a decrease in the nonprotein sulfhydryl content was observed with decreased gastroprotective effects of verapamil.