Effects of Sucralfate and Its Components on Acid- and Pepsin-Induced Damage to Rat Gastric Epithelial Cells.

Abstract

ABSTRACT-Wehave established models of cell damage induced by acid and pepsin using rat gastric epithelial cells (RGMI). In the present study, the effects of aluminum hydroxide [AI(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 10010 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 50010; 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.

Complementarity of in vitro and in vivo models for the evaluation of gastro-protective effects of pharmacological substances

“…These diverging results are discussed further below. In contrast with our data, some authors have shown an increase of gastric mitochondrial function using the MTT assay, following concomitant incubation with sucralfate and indomethacin . These contradictory findings could be explained by differences between several parameters including the concentration of MTT, the duration of incubation, or the number of viable cells and their metabolic activity.…”

Effects of Sucralfate on Gastric Irritant-Induced Necrosis and Apoptosis in Cultured Guinea Pig Gastric Mucosal Cells.

“…In addition to its ability to induce PG synthesis, 18,19) this drug was shown to adhere to gastric mucosa directly and form a physical barrier against gastric irritants, 20,21) which distinguish it from the actions of other gastroprotective drugs. In addition to various mechanisms for its cytoprotective effects, such as detoxification and stimulation of mucus secretion and synthesis, [22][23][24] sucralfate was shown to protect gastric mucosal cells from gastric irritants (NSAIDs and taurocholate) directly in vitro, 25,26) suggesting that this drug can inhibit the processes of necrosis and apoptosis. In this study, we found that sucralfate inhibits gastric irritant-induced necrosis in vitro.…”

A thin layer of sucrose octasulfate protects the oesophageal mucosal epithelium in reflux oesophagitis

“…In an ethanol-induced gastric injury model, the efficacy of SOS was reported to be weaker than that of sucralfate 26 . Additionally, an in vitro study showed that treatment with SOS alone cannot alleviate acid damaged-cultured cells 27 . However, several reports have indicated that SOS shows therapeutic effects in various oesophagitis models.…”