Lecithin in mixed micelles attenuates the cytotoxicity of bile salts in Caco-2 cells

被引:48
作者
Tan, Ya'nan [1 ,2 ,3 ]
Qi, Jianping [1 ,2 ]
Lu, Yi [1 ,2 ]
Hu, Fuqiang [4 ]
Yin, Zongning [3 ]
Wu, Wei [1 ,2 ]
机构
[1] Fudan Univ, Sch Pharm, Minist Educ, Key Lab Smart Drug Delivery, Shanghai 201203, Peoples R China
[2] Fudan Univ, Sch Pharm, PLA, Shanghai 201203, Peoples R China
[3] Sichuan Univ, West China Sch Pharm, Chengdu 610041, Sichuan, Peoples R China
[4] Zhejiang Univ, Sch Pharm, Hangzhou 310058, Zhejiang, Peoples R China
关键词
Mixed micelles; Bile salt; Lecithin; Caco-2; cells; Cytotoxicity; SOLUBILIZATION; ABSORPTION; PHOSPHATIDYLCHOLINE; MECHANISM; CAPRATE; PLASMA; RATS;
D O I
10.1016/j.tiv.2012.11.018
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
This study was designed to investigate the cytotoxicity of bile salt-lecithin mixed micelles on the Caco-2 cell model. Cell viability and proliferation after mixed micelles treatments were evaluated with the MTT assay, and the integrity of Caco-2 cell monolayer was determined by quantitating the transepithelial electrical resistance and the flux of tracer, FITC-dextran 4400. The apoptosis induced by mixed micelles treatments was investigated with the annexin V/PI protocol. The particle size of mixed micelles was all smaller than 100 nm. The mixed micelles with lower than 0.2 mM sodium deoxycholate (SDC) had no significant effects on cell viability and proliferation. When the level of SDC was higher than 0.4 mM and the lecithin/SDC ratio was lower than 2:1, the mixed micelles caused significant changes in cell viability and proliferation. Furthermore, the mixed micelles affected tight junctions in a composition-dependent manner. Specifically, the tight junctions were transiently opened rather than damaged by the mixed micelles with SDC of between 0.2 and 0.6 mM. The mixed micelles with more lecithin also induced less apoptosis. These results demonstrate that relatively higher concentrations of mixed micelles are toxic to Caco-2 cells, while phospholipids can attenuate the toxicity of the bile salts. Crown Copyright (C) 2012 Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:714 / 720
页数:7
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