LECITHIN PROTECTS AGAINST PLASMA-MEMBRANE DISRUPTION BY BILE-SALTS

Introduction. Detergent disruption of epithelial plasma membranes by b ile salts may contribute to pathogenesis of cholestasis and gastroesop hageal reflux disease. Bile, despite containing high concentrations of bile salts, normally is not toxic to biliary or intestinal epithelia. We hypothesize that lecithin in bile may protect cell membranes from disruption by bile salts. Methods. We studied the interactions of taur ine conjugates of ursodeoxycholate (TUDCA), cholate (TCA), chenodeoxyc holate (TCDCA), and deoxycholate (TDCA) with erythrocyte plasma membra nes with or without large unilamellar egg lecithin vesicles for variou s times at 23 degrees C. Release of hemoglobin was quantified spectrop hotometrically. The concentration of bile salt monomers and simple mic elles in the intermixed micellar aqueous phase (TMMC) was determined b y centrifugal ultrafiltration. Results. The degree of hemolysis depend ed on the hydrophobicity of the bile salts and was progressive over ti me. Addition of lecithin reduced the hemolytic effects of 20 mM TCA or 2 mM TDCA in a concentration-dependent manner at both 30 min and 4 h. Increasing the concentration of lecithin progressively reduced the IM MC of TDCA. Hemolysis following addition of lecithin to 2 mM TDCA was comparable to hemolysis produced by lecithin-free TDCA solutions when diluted to similar IMMC values. Conclusion. We conclude that lecithin reduces plasma membrane disruption by hydrophobic bile salts. This pro tection may be attributable to association of bile salts with vesicles and mixed micelles, reducing the concentration of bile salt monomers and simple micelles available to interact with cell membranes. Lecithi n may play a key role in preventing bile salt injury of biliary and ga strointestinal epithelia. (C) 1998 Academic Press.