Study of the damaging effects of acetazolamide on gastric mucosa in rats.
The present study demonstrated that acetazolamide (100 and 200 mg/kg, s.c.) induced severe gastric hemorrhagic ulceration in rats. The ulceration was aggravated by oral administration of HCl, but was inhibited by NaHCO3. Furthermore, the severity of ulceration was also decreased by pretreatment with methysergide, chlorpheniramine, or cimetidine. These protective effects were accompanied by an increase in serotonin and histamine released from the stomach. Acetazolamide injection also increased the protein level but reduced the sialic acid content in the gastric secretion, indicating that the gastric mucosal barrier may have been damaged. Prostaglandin E2 content of the gastric mucosa was not affected by the drug; however, carbonic anhydrase activity was markedly reduced in a dose-dependent manner. Thus, it is suggested that the ulceration induced by acetazolamide is mainly due to the inhibition of carbonic anhydrase activity and mucus secretion. The increase in serotonin and histamine release also may have been the contributing factors for gastric ulcer formation.
D000086:Acetazolamide / Q000633:toxicity*; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D002257:Carbonic Anhydrase Inhibitors / Q000633:toxicity; D002256:Carbonic Anhydrases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000201:enzymology / Q000517:prevention & control
D000897:Anti-Ulcer Agents; D002257:Carbonic Anhydrase Inhibitors; D002256:Carbonic Anhydrases; D000086:Acetazolamide