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• W1967843721 abstract "The bile salts (BS) cholate (C) and 12-monoketocholate (12-MKC) have been shown to inhibit the transcellular permeation of methotrexate (MTX) across Caco-2 cell monolayers. The aim of this study was to investigate the mechanism of this inhibition by comparing the effects of C, 7-MKC, 12-MKC, 3,7-diketocholate (DKC) and triketocholate (TKC) on MTX uptake by Caco-2 cells. Critical micelle concentrations (CMCs) and cytotoxicities of BS and their effects on membrane fluidity Caco-2 cells were determined by standard methods. MTX uptake by Caco-2 cell monolayers was determined using LC–MS/MS. Replacing hydroxyl groups in C with keto groups and changing from 7-MKC to 12-MKC resulted in BS with lower cytotoxicity, higher CMC and decreased ability to inhibit the uptake of MTX. 7- and 12-MKC increased membrane fluidity of hydrophilic regions of Caco-2 cell membranes, DKC and TKC increased membrane fluidity of hydrophobic regions and C had little effect on membrane fluidity of either region. Replacing hydroxyl groups in C with keto groups produces BS with different physicochemical properties and biological effects. Since ketocholates (but not C) decrease MTX uptake in parallel with increasing membrane fluidity, it is suggested that ketocholates inhibit MTX influx transporters indirectly through disturbing their lipid environment." @default.
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• W1967843721 date "2012-08-01" @default.
• W1967843721 modified "2023-09-26" @default.
• W1967843721 title "Effect of ketocholate derivatives on methotrexate uptake in Caco-2 cell monolayers" @default.
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• W1967843721 doi "https://doi.org/10.1016/j.ijpharm.2012.04.077" @default.
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