title: Lecithin in mixed micelles attenuates the cytotoxicity of bile salts in Caco-2 cells.
abstract: 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 0.2mM sodium deoxycholate (SDC) had no significant effects on cell viability and proliferation. When the level of SDC was higher than 0.4mM 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 0.6mM. 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.
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, School of Pharmacy, Fudan University, Shanghai 201203, China.
authors.forename: Ya'nan
authors.initials: Y
authors.lastname: Tan
authors.forename: Jianping
authors.initials: J
authors.lastname: Qi
authors.forename: Yi
authors.initials: Y
authors.lastname: Lu
authors.forename: Fuqiang
authors.initials: F
authors.lastname: Hu
authors.forename: Zongning
authors.initials: Z
authors.lastname: Yin
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
mesh_terms: D017209:Apoptosis; D018938:Caco-2 Cells; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003840:Deoxycholic Acid / Q000008:administration & dosage / Q000633:toxicity*; D006801:Humans; D054709:Lecithins / Q000008:administration & dosage / Q000633:toxicity*; D008823:Micelles
chemical_list: D054709:Lecithins; D008823:Micelles; D003840:Deoxycholic Acid