Effects of sucralfate on acute gastric mucosal injury and gastric ulcer induced by ischemia-reperfusion in rats.
We have revealed that acute gastric mucosal injury induced by a single ischemia-reperfusion (I-R) treatment develops into an ulcerative lesion within a few days. In the present studies, we examined the effects of oral administration of sucralfate on gastric damage induced by I-R. Sucralfate (1-100 mg/kg, 15 min before I-R) significantly reduced the total erosion area observed immediately after I-R. A high dose of sucralfate (30-100 mg/kg) inhibited the increase in the thiobarbituric acid-reactive substances, an index of lipid peroxidation, induced by I-R, although a low dose of it failed. When sucralfate (30 mg/kg, once a day) was orally administered after I-R, it prevented mucosal damage from developing into gastric ulcers: the total area of the ulcers was significantly reduced compared to that without sucralfate administration 72 h after I-R. High concentrations of sucralfate (3-10 mg/ml) reduced the superoxide radicals generated by leukocytes or xanthine-xanthine oxidase, and protected erythrocyte membrane ghosts against lipid peroxidation induced by hydrogen peroxide and Fe2+ in vitro. These results indicate that sucralfate may prohibit both the generation of acute gastric mucosal injury and its progression to ulcer induced by I-R, probably due to a cytoprotective action on the mucosal surface. However, the protective mechanism may involve an inhibitory action on superoxide and hydroxyl radicals at high doses.
Wada
K
K
Department of Clinical Pharmacology, Faculty of Medicine, Tottori University, Yonago, Japan. wadakou@grape.med.tottori-u.ac.jp
Kamisaki
Y
Y
Kitano
M
M
Kishimoto
Y
Y
Nakamoto
K
K
Itoh
T
T
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D004910:Erythrocyte Membrane / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D017665:Hydroxyl Radical; D007962:Leukocytes / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species; D015427:Reperfusion Injury / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D013276:Stomach Ulcer / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D013392:Sucralfate / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism
D000897:Anti-Ulcer Agents; D008054:Lipid Peroxides; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D013481:Superoxides; D017665:Hydroxyl Radical; D013392:Sucralfate; D014969:Xanthine Oxidase