Effects of 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, an inhibitor of Cl(-)-HCO3- exchanger, on stress-induced gastric lesions in rats.
The effect of 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), an inhibitor of Cl(-)-HCO3- exchanger, on stress-induced gastric lesions was studied in rats. The stress exposure to rats was performed by restraint plus water-immersion (22 degrees C) for 6 h. Oral administration of DIDS produced a dose-dependent reduction in the gastric lesion formation. The ED50 value for DIDS was 94.4 mg/kg (64.2 - 138.8 mg/kg; 95% confidence limits) and the maximum effect was observed at the dose of 300 mg/kg with an inhibition of 95%. A dose-dependent reduction in lesions was also observed after administration of omeprazole, an inhibitor of proton pump. The ED50 value for omeprazole was 3.1 mg/kg (1.8 - 5.4 mg/kg; 95% confidence limits) and the effect was maximum at 16 mg/kg with an inhibition of 92%. These results indicated that DIDS protected the gastric mucosa against stress-induced lesions. It is speculated that the antiulcerous activity of DIDS may give a clue for the development of a new class of therapeutic drugs for the prevention and healing of gastric ulcers.
Horie
S
S
Department of Drug Evaluation and Toxicological Sciences, Faculty of Pharmaceutical Sciences, Chiba University, Japan.
Yano
S
S
Watanabe
K
K
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002352:Carrier Proteins / Q000037:antagonists & inhibitors*; D027963:Chloride-Bicarbonate Antiporters; D007101:Immersion; D008297:Male; D009853:Omeprazole / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012149:Restraint, Physical; D013276:Stomach Ulcer / Q000209:etiology / Q000517:prevention & control*; D013315:Stress, Psychological / Q000150:complications*
D002352:Carrier Proteins; D027963:Chloride-Bicarbonate Antiporters; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D009853:Omeprazole; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid