Ulcer formation and cytoprotection by acetazolamide.
Acetazolamide, a carbonic anhydrase inhibitor, was administered orally and subcutaneously to rats. Acetazolamide increased the gastric ulcerogenicity of indomethacin, but inhibited gastric ulcers produced by acidified aspirin. When administered alone to fasted rats, it did not produce gastric ulcers. Acetazolamide was also cytoprotective for the stomach (it reduced dose dependently the number of gastric necrotic lesions caused by absolute ethanol given orally) and for the small intestine (it prevented dose dependently intestinal lesions produced by administration of a high dose of indomethacin). Acetazolamide did not prevent the antiulcer effect of PGE2 (against aspirin-induced ulcers) nor the cytoprotective effect of 16,16-dimethyl PGE2 (against ethanol-induced gastric lesions). The degree of gastric cytoprotection increased with time after a single administration of acetazolamide; the optimal effect occurred 60 and 90 min after oral and subcutaneous administration, respectively. Pretreatment with indomethacin completely prevented the cytoprotective effect of acetazolamide; this suggests that the cytoprotective effect may be mediated by endogenous release of prostaglandins by the stomach. All the effects of acetazolamide reported here were observed after either oral or subcutaneous administration. The mechanism by which acetazolamide influences ulcer formation and is cytoprotective is unknown.
D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology; D000086:Acetazolamide / Q000494:pharmacology*; D000818:Animals; D001241:Aspirin / Q000633:toxicity; D015232:Dinoprostone; D000431:Ethanol / Q000009:adverse effects; D005260:Female; D005753:Gastric Mucosa / Q000473:pathology; D007213:Indomethacin / Q000633:toxicity; D011458:Prostaglandins E / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control; D013997:Time Factors
D011458:Prostaglandins E; D000431:Ethanol; D015232:Dinoprostone; D015064:16,16-Dimethylprostaglandin E2; D000086:Acetazolamide; D001241:Aspirin; D007213:Indomethacin