Effects of Sucralfate and Its Components on Acid- and Pepsin-Induced Damage to Rat Gastric Epithelial Cells
Osamu Furukawa (1), Hiroshi Matsui (2) and Noriko Suzuki (1)
(1) Department of Applied Pharmacology, Kyoto Pharmaceutical University,
Misasagi, Yamashina, Kyoto 607, Japan
(2) Department of Gastroenterology, Institute of Clinical Medicine, Tsukuba
University 1-1-1, Tennodai, Tsukuba, Ibaraki 305, Japan
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.
Keywords: Sucralfate, Aluminum hydroxide, Potassium sucrose octasulfate,
Rat gastric epithelial cell (RGM1), Cell damage