Anti-ulcer effects of antioxidants: effect of probucol.
We investigated the effect of probucol, a lipid-lowering agent with antioxidant properties, on HCl plus ethanol-induced gastric mucosal injury and on the healing of acetic acid-induced gastric ulcers in rats. When the free radical-scavenging activity of probucol was measured by an electron spin resonance technique, the agent (10(-5)-10(-3) M) scavenged both superoxide anions and hydroxyl radicals. Oral administration of probucol (250-1000 mg/kg) dose dependently prevented the HCl plus ethanol-induced gastric mucosal injury and the increase in thiobarbituric acid-reactive substances, an index of lipid peroxidation, in the injured mucosa. Repeated oral administration of probucol (250-1000 mg/kg twice daily) dose dependently accelerated the healing of acetic acid-induced gastric ulcers. In addition, probucol already inhibited the increase in the content of thiobarbituric acid-reactive substances in the ulcerated region before the ulcer-healing effect of this agent was recognized. These results suggest that probucol may partly protect gastric mucosa from acute gastric mucosal injury and promote the healing of chronic gastric ulcers by its antioxidant activity.
Ito
M
M
Department of Pharmacology, Faculty of Pharmacy, Meijo University, Nagoya, Japan.
Suzuki
Y
Y
Ishihara
M
M
Suzuki
Y
Y
D019342:Acetic Acid; D000208:Acute Disease; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D002908:Chronic Disease; D002927:Cimetidine / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004578:Electron Spin Resonance Spectroscopy; D000431:Ethanol; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects; D006851:Hydrochloric Acid; D017665:Hydroxyl Radical / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009853:Omeprazole / Q000494:pharmacology / Q000627:therapeutic use; D011341:Probucol / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013997:Time Factors
D000897:Anti-Ulcer Agents; D000975:Antioxidants; D016166:Free Radical Scavengers; D017392:Thiobarbituric Acid Reactive Substances; D013481:Superoxides; D017665:Hydroxyl Radical; D000431:Ethanol; D002927:Cimetidine; D009853:Omeprazole; D011341:Probucol; D019342:Acetic Acid; D006851:Hydrochloric Acid