Bile Salt- and Lysophosphatidylcholine-induced Membrane Damage in Human Erythrocytes

Abstract

Abstract The interaction of bile salts and lysophosphatidylcholine (LPC) with membranes has implications both in understanding the aetiology of a number of gastrointestinal disorders, including gastritis, gastric ulcers and colonic cancer, and in enhancing drug absorption by various epithelia. The membrane toxicity of nine bile salts (the sodium (S) salts of chenodeoxycholate (CDC), deoxycholate (DC) and cholate (C) and their glycine (G) and taurine (T) conjugates) and LPC was determined using erythrocyte haemolysis as a model parameter. Washed human erythrocytes were incubated for 15–60 min at 20°C with media buffered at pH 8, 7 and 6. Bile salt toxicity was shown to be a function of type, concentration, pH and contact time with the membrane. At pH 7 toxicity decreased in the order LPC > unconjugated dihydroxy salts (SDC and SCDC) > conjugated deoxycholates (SGDC and STDC) > conjugated chenodeoxycholates (SGCDC and STCDC) > unconjugated trihydroxy salt (SC) > conjugated trihydroxy salts (SGC and STC). Incubation with equimolar combinations of bile salts (SDC + SCDC; STCDC + SGDC; SDC + STDC) indicated that the resultant damage was an additive function of the damage induced by the individual bile salts.