Detergent properties do not fully explain the barrier disruption induced by bile salts

Detergent properties of bile salts are thought to account for their capacity to damage the gastrointestinal mucosa. Bile salts are thought to disrupt the mucosal barrier by dissolving the lipid components of cell membranes. We tested this hypothesis by comparing deoxycholate to several classes of detergents (anionic, nonionic, zwitterionic, cationic) in an in vivo perfused rabbit model of esophagitis. Barrier disruption was indicated by elevated transmucosal fluxes of glucose, calcium and potassium. Detergent strength was measured by the in vitro release of [3H]cholesterol from a mixture of phosphatidylcholine and cholesterol after 1 h of agitation at 37°C and pH 7.4. We found that all detergents significantly solubilized cholesterol in vitro. The nonionic agents were strong detergents, but did not disrupt the esophageal mucosal barrier. The ionic detergents were also strong detergents, but caused significant barrier disruption in vivo. We conclude that the barrier-disrupting capacity of bile salts is not related to their detergent properties per se, but rather to some other physiochemical property not yet determined.