Gastroprotective effect of intragastric clarithromycin against damage induced by ethanol in rats.
Intragastric administration of clarithromycin, a macrolide antibiotic, macroscopically protected the rat gastric mucosa from 96% ethanol-induced lesions. This protective effect was dose-dependent, the reduction being 92.3, 81.4, 52.2, and 5.4% at doses of 400, 200, 100, and 50 mg/kg, respectively. Clarithromycin protection was not significantly modified by pretreatment with either subcutaneous indomethacin (5 mg/kg), a selective cyclooxygenase inhibitor, or iodoacetamide (100 mg/kg), a specific sulfhydryl blocker. Gastric motor activity, measured by the balloon method, was inhibited by clarithromycin in a dose-dependent fashion. The inhibited gastric motor activity induced by clarithromycin was not modified by pretreatment with either indomethacin or iodoacetamide. Ethanol (1 ml/rat, gavage needle) induced hemorrhagic bandlike lesions in the mucosa of the glandular stomach along the long axis of the greater curvature with the occurrence of a complete inhibition of gastric motor activity. This inhibition was not modified by pretreatment with clarithromycin, indomethacin, or iodoacetamide. There was an increase in the fluid volume for clarithromycin at 100, 200, and 400 mg/kg at 30 min and in the mucus volume only for clarithromycin at 400 mg/kg at 30 min. Gastric mucosal blood flow was absent in the ethanol-induced lesions but in the nonlesion areas was the same in clarithromycin-pretreated and vehicle-pretreated rats as in control (no ethanol) rats. Clarithromycin protection was significantly diminished, although not completely abolished by subcutaneous yohimbine (5 mg/kg), a selective alpha2-adrenoceptor antagonist. Yohimbine also significantly reduced both basal and clarithromycin-stimulated gastric mucus secretion. Our data support the conclusion that the protective effect of intragastric clarithromycin was not mediated by endogenous prostaglandins, sulfhydryl compounds of the gastric mucosa, or changes in the gastric contractile patterns. The protection may be the result of an increase in both the fluid volume and the mucus volume retained in the gastric lumen. alpha2-Adrenoceptors possibly are involved by the mucus-dependent mechanism.
Gutiérrez-Cabano
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CA
Department of Surgical Pathology II, Faculty of Medical Sciences, National University of Rosario, Argentina.
Raynald
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AC
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001834:Body Water / Q000187:drug effects; D017291:Clarithromycin / Q000008:administration & dosage* / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D000431:Ethanol; D005260:Female; D005753:Gastric Mucosa / Q000098:blood supply / Q000473:pathology; D005766:Gastrointestinal Contents / Q000187:drug effects; D005769:Gastrointestinal Motility / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology; D007460:Iodoacetamide / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D013270:Stomach / Q000187:drug effects*; D013272:Stomach Diseases / Q000139:chemically induced* / Q000473:pathology; D013439:Sulfhydryl Reagents / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D000900:Anti-Bacterial Agents; D016861:Cyclooxygenase Inhibitors; D013439:Sulfhydryl Reagents; D015016:Yohimbine; D000431:Ethanol; D017291:Clarithromycin; D007213:Indomethacin; D007460:Iodoacetamide