Duodenal ulcers induced by diethyldithiocarbamate, a superoxide dismutase inhibitor, in the rat: role of antioxidative system in the pathogenesis.
Pathogenesis of duodenal ulcers induced by diethyldithiocarbamate (DDC), a superoxide dismutase (SOD) inhibitor, was investigated in the rat. Repeated s.c. administration of DDC (750 mg/kg) every 12 hr induced duodenal ulcers in the fed rats, and the severity of the ulcers reached the maximum after three injections. DDC not only reduced basal acid output but also impaired duodenal alkaline secretion. These ulcers were significantly prevented by antioxidative agents such as SOD (50000 units/kg, s.c.), allopurinol (50 mg/kg, s.c.) or glutathione (200 mg/kg, s.c.) as well as the antisecretory agent cimetidine (100 mg/kg, s.c.). The impaired HCO3- response caused by DDC was partially but significantly reversed by either SOD (15000 units/kg/hr, i.v.), allopurinol or glutathione; and SOD by itself significantly elevated the rate of basal alkaline secretion. 16,16-Dimethyl prostaglandin E2 (10 micrograms/kg, s.c.) increased duodenal HCO3- output in the presence of DDC and significantly prevented the development of duodenal ulcers in response to DDC. These results suggest that the mucosal antioxidative system including SOD may play a role in the regulatory process of alkaline secretion and contribute to the mucosal defensive ability in the duodenum. The insufficiency of this system may be involved in the pathogenesis of DDC-induced duodenal ulcers.
Takeuchi
K
K
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.
Nishiwaki
H
H
Niida
H
H
Ueshima
K
K
Okabe
S
S
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D004050:Ditiocarb; D004381:Duodenal Ulcer / Q000139:chemically induced* / Q000503:physiopathology; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism; D005744:Gastric Acid / Q000378:metabolism; D005978:Glutathione / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D000975:Antioxidants; D000493:Allopurinol; D004050:Ditiocarb; D013482:Superoxide Dismutase; D005978:Glutathione