title: Effects of sucralfate and its components on acid- and pepsin-induced damage to rat gastric epithelial cells.
abstract: We have established models of cell damage induced by acid and pepsin using rat gastric epithelial cells (RGM1). In the present study, the effects of aluminum hydroxide [Al(OH)3] and potassium sucrose octasulfate (KSOS), which are components of sucralfate, and sucralfate on cell damage and peptic activity of pepsin were examined. Pretreatment of cells with sucralfate (0.1-3 mg/ml) or Al(OH)3 (0.1-1 mg/ml) for 2 hr prevented both acid- (pH 4.0) and pepsin- (pH 4.5) induced cell damage. However, KSOS (0.1-1 mg/ml) did not show any effects on two different types of cell damage. The peptic activity of pepsin at pH 4.5 was about 10% of that at pH 2.0. Sucralfate and KSOS slightly inhibited peptic activity at pH 4.5. Al(OH)3 inhibited peptic activity by approximately 50%; however, no concentration-dependent pattern was observed. Pepstatin (0.003-0.1 mg/ml), a specific inhibitor of pepsin, inhibited the peptic activity in a concentration-dependent manner. Here, we confirmed that sucralfate and Al(OH)3 have cytoprotective effects against acid- and pepsin-induced cell damage. The mechanism behind the cytoprotective effects of sucralfate seems to relate to adhesion of the cell surface and neutralization of hydrogen ion by aluminum that prevents the penetration of hydrogen ions into the cells.
authors.affiliation: Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.
authors.forename: O
authors.initials: O
authors.lastname: Furukawa
authors.forename: H
authors.initials: H
authors.lastname: Matsui
authors.forename: N
authors.initials: N
authors.lastname: Suzuki
mesh_terms: D000143:Acids / Q000009:adverse effects*; D000536:Aluminum Hydroxide / Q000494:pharmacology*; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects* / Q000473:pathology; D005753:Gastric Mucosa / Q000166:cytology* / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D010434:Pepsin A / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D010436:Pepstatins / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D013392:Sucralfate / Q000737:chemistry / Q000494:pharmacology*; D013395:Sucrose / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000143:Acids; D000897:Anti-Ulcer Agents; D010436:Pepstatins; D011480:Protease Inhibitors; D013392:Sucralfate; D013395:Sucrose; D000536:Aluminum Hydroxide; D010434:Pepsin A; C053081:sucrose octasulfate