Protection against hydrophobic bile salt-induced cell membrane damage by liposomes and hydrophilic bile salts.
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.
First Department of Internal Medicine, Hiroshima University School of Medicine, Japan.
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H
Sagawa
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S
Tazuma
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Kajiyama
D001647:Bile Acids and Salts / Q000494:pharmacology* / Q000633:toxicity; D002462:Cell Membrane / Q000187:drug effects / Q000648:ultrastructure; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000166:cytology* / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects*; D006801:Humans; D007700:Kinetics; D008081:Liposomes / Q000494:pharmacology*; D010713:Phosphatidylcholines / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013997:Time Factors
D001647:Bile Acids and Salts; D008081:Liposomes; D010713:Phosphatidylcholines