Gastric mucosal protection by acetazolamide in rats. Roles of prostaglandins, sulfhydryls, and gastric motility.
The aim of this study was to test the hypothesis that protective effect of subcutaneous acetazolamide, a carbonic anhydrase inhibitor, against ethanol-induced gastric mucosal damage is dependent on indomethacin- or iodoacetamide-sensitive mechanisms. In addition we studied the effects of acetazolamide on gastric motility and the influence of indomethacin and iodoacetamide on this parameter. Indomethacin (30 mg/kg) or iodoacetamide (100 ag/kg) was administered subcutaneously in doses that previously had been demonstrated to inhibit endogenous prostaglandins synthesis and gastric mucosal sulfhydryls respectively. At 30 min after these or control subcutaneous pretreatment, the rats were given subcutaneous acetazolamide or vehicle. Thirty min later 96% ethanol was administered orally and the rats were sacrificed 60 min after ethanol administration. The lesions of the gastric glandular mucosa were measured in length and width and expressed in square millimeters. Gastric motility was recorded by a balloon method. The results showed that neither indomethacin nor iodoacetamide aggravated ethanol-induced gastric mucosal damage. The protective effect of subcutaneous acetazolamide was suppressed by pretreatment with indomethacin but not with that of iodoacetamide. Acetazolamide inhibited gastric motility in a dose-dependent fashion. The inhibited gastric motility induced by acetazolamide was reversed by indomethacin but not by iodoacetamide. A highly significant relationship was found between the inhibitory effect of acetazolamide on the motor activity and the mucosal lesions (r +/- 0.8777, P < 0.01). We conclude that the mechanism mediating subcutaneous acetazolamide protection against 96% ethanolinduced gastric mucosal lesions is dependent on indomethacin- and independent of iodoacetamide sensitive mechanisms.
Gutiérrez-Cabano
C A
CA
Department of Surgical Pathology II, Faculty of Medical Sciences, National University of Rosario, Argentina.
D000086:Acetazolamide / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000009:adverse effects / Q000037:antagonists & inhibitors; D005260:Female; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D007213:Indomethacin / Q000494:pharmacology; D007279:Injections, Subcutaneous; D007460:Iodoacetamide / Q000494:pharmacology; D008297:Male; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013438:Sulfhydryl Compounds / Q000502:physiology*; D013997:Time Factors
D011453:Prostaglandins; D013438:Sulfhydryl Compounds; D000431:Ethanol; D000086:Acetazolamide; D007213:Indomethacin; D007460:Iodoacetamide