Cytoprotection by sucralfate: Role of sulfate ions

Sucralfate and its component, sucrose octasulfate, are both SO₄^2--containing compounds shown to protect against acid-peptic injury in rabbit and/or cat esophagi. To determine if sulfate ions (SO₄^2-) contributed to this protection, a series of in vitro and in vivo experiments were performed in acid-exposed rabbit esophagi. In the Ussing chamber SO₄^2--containing solutions significantly reduced the acid-induced decline in electrical resistance (R) observed in controls. This effect was unrelated to buffering of H⁺, accompanying cation or changes in luminal solution osmolality. Protection by SO₄^2- was specific since other divalent (HPO₄^2-) or impermeant anions (gluconate^-) failed to reduce the acid-induced decline in R. Protection was confirmed in vivo by showing that acid-perfused esophagi exposed to SO₄^2- had less morphologic damage, higher R and lower permeability to ¹⁴C-mannitol and H⁺ than controls. These results indicate that SO₄^2- have a unique protective action against acid injury to esophagal epithelia, and this action appears to explain the cytoprotective properties of sucralfate.