Protection against hydrophobic bile salt-induced cell membrane damage by liposomes and hydrophilic bile salts

Abstract

Under physiological circumstances, cell membrane damage is not evident in biliary systems, despite the fact that hydrophobic bile salts are known to induce such damage by their detergent effects. The aim of this study was to determine the cytoprotective effects of liposomes and hydrophilic bile salts against hydrophobic bile salt-induced cell membrane damage, with the use of hemolysis of erythrocytes as a model of cytotoxicity. Washed human erythrocytes were incubated for 10, 30, 60, 90, and 120 min in buffered media (pH 7.45) containing increasing concentrations of different bile salts (1, 2.5, 5, 25, 50 mM). The cytotoxicity of the bile salts was found to be dose and time dependent and was correlated to the degree of the hydrophobicity of the bile salts as determined by the retention factor in reversed-phase high-performance liquid chromatography. Hydrophobic bile salt-induced hemolysis was reduced by liposomes and hydrophilic bile salts. Cytoprotection by liposomes was related to the degree of saturation of the fatty acyl chains, and cytoprotection by hydrophilic bile salts was related to their hydrophilicity. These in vitro findings indicate that vesicles may play a role in protection against cell membrane damage by hydrophobic bile salts in biliary systems and that such damage may be caused by an imbalance between hydrophobic and hydrophilic bile salts.

Characterization of Enantiomeric Bile Acid-induced Apoptosis in Colon Cancer Cell Lines

“…Increased apoptosis from the hydrophobic bile acids may result from more rapid diffusion across the cell membrane or increased accumulation within hydrophobic regions of the cell, such as lipid bilayers. These results are also consistent with other literature reports demonstrating that bile acid hydrophobicity is proportional to cellular toxicity (3,50,51).…”

Regulation of MDR2 P-glycoprotein expression by bile salts

“…Increased phospholipid secretion at the same rate of bile salt secretion could be caused by the greater phospholipid-extracting capacity of the more hydrophobic taurocholate compared with the more hydrophilic tauromuricholate and TUDC [3,17], or by increased mdr2 expression. In order to distinguish between these factors, we studied phospholipid secretion in control and cholatefed mice after complete replacement of the endogenous bile salt pool by TUDC infusion.…”

“…On the one hand, it provides a route by which cholesterol can leave the body and, on the other, it decreases the detergent action of the bile salts that are present in high concentrations in the biliary tree (reviewed in [1]). In model systems the presence of phospholipids and cholesterol greatly decreases the cytotoxic action of bile salts [2,3].…”

Bezafibrate stimulates canalicular localization of NBD-labeled PC in HepG2 cells by PPARα-mediated redistribution of ABCB4

“…This protects the biliary epithelium from the detergent action of hydrophobic bile acids (1), which are present at high concentrations in the biliary tree (2,3).…”