Effects of sucralfate, lansoprazole, and cimetidine on the delayed healing by hydrocortisone sodium phosphate of chronic gastric ulcers in the rat.
We have previously shown that chronic sucralfate ingestion stimulates gastric epithelial proliferation in rats, which may explain one of the beneficial effects of sucralfate in healing of peptic ulcers. In a separate study, we have found that chronic steroid administration delays the healing of experimental gastric ulcers in rats. This study was designed to test the beneficial effects of sucralfate, cimetidine, and lansoprazole (AG-1749, a new proton pump inhibitor), on the delayed healing by steroids in rat chronic gastric ulcers. Chronic gastric ulcers were produced in male Wistar rats, weighing 180 g, by the application of 100% acetic acid. The rats were randomly divided into five groups; (1) control, (2) vehicle alone, (3) 10 mg/kg lansoprazole, (4) 500 mg/kg sucralfate, and (5) 100 mg/kg cimetidine. Except for controls, all rats received daily intraperitoneal injections of 2.5 mg/kg hydrocortisone sodium phosphate. Tested drugs were administered intragastrically (lansoprazole and sucralfate) or intraperitoneally (cimetidine) twice a day for 2 weeks. Rats were sacrificed 14 days later and ulcer size was measured. Chronic administration of hydrocortisone sodium phosphate resulted in a significant delay of ulcer healing induced by acetic acid. Treatment with either lansoprazole or sucralfate abolished the deleterious effect of steroids, whereas cimetidine had no effect. These results indicate that lansoprazole and sucralfate overcome the delayed healing by steroids of chronic gastric ulcers in the rat.
Kuwayama
H
H
Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
Matsuo
Y
Y
Eastwood
G L
GL
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000085:Acetates / Q000009:adverse effects; D019342:Acetic Acid; D000818:Animals; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D002927:Cimetidine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D006854:Hydrocortisone / Q000009:adverse effects*; D064747:Lansoprazole; D008297:Male; D009853:Omeprazole / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D013392:Sucralfate / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D014945:Wound Healing / Q000187:drug effects*
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000085:Acetates; D000897:Anti-Ulcer Agents; D064747:Lansoprazole; D013392:Sucralfate; D002927:Cimetidine; D009853:Omeprazole; D019342:Acetic Acid; D006854:Hydrocortisone