Sphingomyelin exhibits greatly enhanced protection compared with egg yolk phosphatidylcholine against detergent bile salts

Inclusion of phosphatidylcholine within bile salt micelles protects against bile salt-induced cytotoxicity. In addition to phosphatidylcholine, bile m ay contain significant amounts of sphingomyelin, particularly under cholest atic conditions. We compared protective effects of egg yolk phosphatidylcho line (similar to phosphatidylcholine in bile), egg yolk sphingomyelin (main ly 16:0 acyl chains) and dipalmitoyl phosphatidylcholine against taurochola te iu complementary in vitro studies. Upon addition of taurocholate-contain ing micelles to sonicated egg yolk phosphatidylcholine vesicles, subsequent micellization of the vesicular bilayer proved to be retarded when phosphol ipids had also been included in these micelles in the rank order: egg yolk phosphatidylcholine < dipalmitoyl phosphatidylcholine < sphingomyelin, Hemo lysis of erythrocytes and LDH release by CaCo-2 cells after addition of tau rocholate micelles were strongly reduced by including small amounts of sphi ngomyelin or dipalmitoyl phosphatidylcholine in these micelles (PL/(PL + BS ) greater than or equal to 0.1), whereas egg yolk phosphatidylcholine provi ded less protection. Amounts of non-phospholipid-associated bile salts (tho ught to be responsible for cytotoxicity) in egg yolk phosphatidylcholine-co ntaining micelles were significantly higher than in corresponding sphingomy elin-or dipalmitoyl phosphatidylcholine-containing micelles (tested at PL/( PL + BS) ratios 0.1, 0.15, and 0.2). LDH release upon incubation of CaCo-2 cells with taurocholate simple micelles at these so-called "intermixed mice llar-vesicular" concentrations was identical to LDH release upon incubation with corresponding taurocholate-phospholipid mixed micelles. jlr In conclu sion, we found greatly enhanced protective effects of sphingomyelin and dip almitoyl phosphatidylcholine compared to egg yolk phosphatidylcholine again st bile salt-induced cytotoxicity, related to different amounts of non-phos pholipid-associated bile salts. These findings may be relevant for protecti on against bile salt-induced cytotoxicity in vivo.