Lecithin protects against plasma membrane disruption by bile salts.
BACKGROUND
Detergent disruption of epithelial plasma membranes by bile salts may contribute to pathogenesis of cholestasis and gastroesophageal 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 taurine conjugates of ursodeoxycholate (TUDCA), cholate (TCA), chenodeoxycholate (TCDCA), and deoxycholate (TDCA) with erythrocyte plasma membranes with or without large unilamellar egg lecithin vesicles for various times at 23 degreesC. Release of hemoglobin was quantified spectrophotometrically. The concentration of bile salt monomers and simple micelles in the intermixed micellar aqueous phase (IMMC) was determined by centrifugal ultrafiltration.


RESULTS
The degree of hemolysis depended on the hydrophobicity of the bile salts and was progressive over time. 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 IMMC 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.


CONCLUSIONS
We conclude that lecithin reduces plasma membrane disruption by hydrophobic bile salts. This protection 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. Lecithin may play a key role in preventing bile salt injury of biliary and gastrointestinal epithelia.
Narain
P K
PK
Medical College of Virginia of Virginia, Commonwealth University, Richmond, Virginia, USA.
DeMaria
E J
EJ
Heuman
D M
DM
D001647:Bile Acids and Salts / Q000494:pharmacology*; D004910:Erythrocyte Membrane / Q000187:drug effects* / Q000378:metabolism*; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D006461:Hemolysis / Q000187:drug effects / Q000502:physiology; D006801:Humans; D010713:Phosphatidylcholines / Q000378:metabolism / Q000494:pharmacology*; D010743:Phospholipids / Q000378:metabolism; D013501:Surface-Active Agents / Q000494:pharmacology
D001647:Bile Acids and Salts; D005765:Gastrointestinal Agents; D010713:Phosphatidylcholines; D010743:Phospholipids; D013501:Surface-Active Agents