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 gallopamil was studied. All three drugs reduced cold-restraint stress-induced ulcer development. Gallopamil almost abolished gastric ulcers. Verapamil prevented the increase in gastric lipid peroxidation (LP) due to stress. On the other hand, devapamil and gallopamil increased gastric lipid peroxidation and decreased glutathione levels. This effect may be attributed to the increase in oxygen supply due to possible effective vasodilation at gastric mucosa. The second part of this study revealed that stress-induced gastric ulcers in rats rapidly and spontaneously heal and disappear within 24 h. During recovery, gastric LP decreased and glutathione levels increased within 12 h after the withdrawal of stress, preceded by an initial reduction in glutathione. After 72 h, an unexplained increase in gastric LP and a decrease in glutathione were observed. Treatment with verapamil, devapamil and gallopamil promoted healing, gallopamil being again the most effective. Their effects on gastric LP and glutathione levels are in accordance with the results of pretreatment experiments. In conclusion, devapamil and gallopamil are effective antiulcer agents against stress-induced ulcers, but unlike verapamil, antioxidant activity does not seem likely to be among their mechanisms of action.
Alican
I
I
Department of Physiology, Marmara University, School of Medicine, Istanbul, Turkey.
Toker
F
F
Arbak
S
S
Yegen
B C
BC
Yalçin
A S
AS
Oktay
S
S
D000818:Animals; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D003080:Cold Temperature; D005260:Female; D005978:Glutathione / Q000187:drug effects* / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051381:Rats; D012149:Restraint, Physical; D013223:Statistics as Topic; D013276:Stomach Ulcer / Q000188:drug therapy* / Q000503:physiopathology*; D013312:Stress, Physiological / Q000503:physiopathology; D013997:Time Factors
D002121:Calcium Channel Blockers; D005978:Glutathione