Importance of an Acid Milieu in the Sucralfate-Induced Gastroprotection against Ethanol Damage

Sucralfate is known for its gastroprotective properties in humans and rats, but the importance of intragastric pH in this protection is a subject of controversy. This study, performed on healthy young volunteers and rats, was designed to compare the gastroprotective effects of sucralfate with those of sucralfate combined with ranitidine or of sucralfate adjusted to pHs varying from 1 to 7. In humans the mucosal damage induced by 40% ethanol spray after 4 days of pretreatment with placebo, sucralfate (1 g four times daily), ranitidine (150 mg three times daily), or the combination of sucralfate plus ranitidine was evaluated by means of endoscopy with mucosal biopsy and histologic examination. Sucralfate alone reduced the endoscopic score significantly (compared with placebo) and prevented deep necrotic lesions. Neither ranitidine alone nor its combination with sucralfate prevented ethanol-induced endoscopic and histologic mucosal changes. In rats acute gastric lesions were induced by 100% ethanol. Sucralfate was relatively more effective in mucosal protection against ethanol when given at lower pH (1 or 2) than at original pH (4.5) and failed to protect at neutral pH (7.0). Pretreatment with ranitidine, which by itself did not change ethanol damage, greatly reduced the protection afforded by sucralfate. We conclude that sucralfate protects the gastric mucosa against ethanol damage both in humans and in rats and that this protection is dependent on the presence of an acidic intragastric pH.