Protective effect of sucralfate against alcohol-induced gastric mucosal injury in the rat. Macroscopic, histologic, ultrastructural, and functional time sequence analysis.
Histologic or ultrastructural evidence of the ability of sucralfate to protect the gastric mucosa against ethanol injury is lacking. Therefore we analyzed morphologic and functional changes in the mucosa of 120 rats receiving, intragastrically, 2 ml of either sucralfate 500 mg/kg body wt or a control solution and 1 h later 2 ml of 100% ethanol. At 15 min, 1, 4, 6, and 24 h after ethanol instillation, mucosal changes were assessed by macroscopic examination, quantitative histology, scanning electron microscopy, recordings of gastric potential difference, and measurements of volume, pH, and electrolytes in the gastric contents. Between 15 min and 24 h after ethanol instillation, macroscopic necrotic lesions in controls involved greater than 33% of mucosal area and in the sucralfate-treated group less than 4% (p less than 0.001 for each period). In controls, ethanol instillation produced surface epithelial cell disruption and deep (greater than 0.2 mm) mucosal necrosis involving greater than 55% +/- 3% of the mucosal length. In sucralfate-pretreated animals, disruption of the surface epithelium was present at 15 min, 1 h, and 4 h after ethanol instillation, but deep necrotic lesions were virtually absent (0%-2%; p less than 0.001 vs. controls) during the entire study period. The surface epithelium was mostly reestablished by 6 h after ethanol instillation in the sucralfate group but not in the controls. We concluded that sucralfate protects the gastric mucosa against ethanol-induced injury by preventing deep mucosal necrosis and as a consequence the mucosal proliferative zone cells rapidly restitute mucosal integrity.
D000535:Aluminum / Q000494:pharmacology*; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D004573:Electrolytes / Q000378:metabolism; D000431:Ethanol / Q000037:antagonists & inhibitors*; D005745:Gastric Acidity Determination; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced / Q000517:prevention & control; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008855:Microscopy, Electron, Scanning; D009336:Necrosis / Q000139:chemically induced / Q000517:prevention & control; D051381:Rats; D011919:Rats, Inbred Strains; D013392:Sucralfate; D013997:Time Factors
D000897:Anti-Ulcer Agents; D004573:Electrolytes; D000431:Ethanol; D013392:Sucralfate; D000535:Aluminum