Pathogenesis of gastric ulceration produced by acetazolamide in rats.
The present experiment demonstrated that relatively high doses of acetazolamide (100 and 200 mg/kg s.c.) induced severe gastric hemorrhagic ulceration in rats. This ulceration was aggravated by oral administration of HC1, but was inhibited by NaHCO3. Further, the severity of ulceration was also decreased by pretreatment with methysergide, chlorpheniramine, or cimetidine. These protective effects were affirmed by an increase in serotonin and histamine released from the stomach after acetazolamide treatment. 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 increases in serotonin and histamine released may also have been contributing factors for gastric ulcer formation.
D000086:Acetazolamide / Q000494:pharmacology / Q000633:toxicity*; D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology; D002257:Carbonic Anhydrase Inhibitors; D015232:Dinoprostone; D004305:Dose-Response Relationship, Drug; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D006633:Histamine Antagonists / Q000494:pharmacology; D008297:Male; D011458:Prostaglandins E / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D012702:Serotonin Antagonists / Q000494:pharmacology; D017693:Sodium Bicarbonate; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000378:metabolism
D001639:Bicarbonates; D002257:Carbonic Anhydrase Inhibitors; D006633:Histamine Antagonists; D011458:Prostaglandins E; D012702:Serotonin Antagonists; D017693:Sodium Bicarbonate; D015232:Dinoprostone; D000086:Acetazolamide