GASTRIC LIPID-PEROXIDATION, GLUTATHIONE AND CALCIUM-CHANNEL BLOCKERS IN THE STRESS-INDUCED ULCER MODEL IN RATS

The antiulcer activity of verapamil and its analogues devapamil and ga llopamil was studied. All three drugs reduced cold-restraint stress-in duced ulcer development. Gallopamil almost abolished gastric ulcers. V erapamil prevented the increase in gastric lipid peroxidation (LP) due to stress. On the other hand, devapamil and gallopamil increased gast ric lipid peroxidation and decreased glutathione levels. This effect m ay be attributed to the increase in oxygen supply due to possible effe ctive vasodilation at gastric mucosa. The second part of this study re vealed that stress-induced gastric ulcers in rats rapidly and spontane ously heal and disappear within 24 h. During recovery, gastric LP decr eased and glutathione levels increased within 12 h after the withdrawa l of stress, preceded by an initial reduction in glutathione. After 72 h, an unexplained increase in gastric LP and a decrease in glutathion e were observed. Treatment with verapamil, devapamil and gallopamil pr omoted healing, gallopamil being again the most effective. Their effec ts on gastric LP and glutathione levels are in accordance with the res ults of pretreatment experiments. In conclusion, devapamil and gallopa mil are effective antiulcer agents against stress-induced ulcers, but unlike verapamil, antioxidant activity does not seem likely to be amon g their mechanisms of action.