Background and Objectives Lithium chloride (LiCl) has been shown to improve the tightness of brain endothelial cell monolayers in vitro by inhibition of the GSK-3b enzyme, activation of the Wnt/beta-catenin pathway and regulation of tight junction (TJ) protein expression. However, the effect of LiCl on the drug transporters and drugmetabolizing enzymes has not been addressed so far. The hCMEC/D3 cell line is a validated in vitro BBB model expressing transporters and drug-metabolizing enzymes (phase 1 and 2). The present study was conducted to compare the mRNAs levels corresponding to several BBB endothelial markers in hCMEC/D3 cells with and without incubation in LiCl. Methods We used quantitative real-time polymerase chain reaction (qRT-PCR) to quantify the mRNA expression of 5 tight junction (TJ) proteins, 4 adhesion proteins, 5 solute carriers, 7 ATP-binding cassette (ABC) transporters, 8 cytochrome P450 (CYP) and 17 phase 2 conjugation enzymes in hCMEC/D3 cells with and without incubation in LiCl. Results Our study showed that LiCl treatment for 6 days at a concentration of 10 mM induced the TJ protein claudin- 3, the ABC transporter BCRP/ABCG2, the cytochrome P-450 CYP1A1 and the glutathione-S-transferase GSTM3, while the other selected markers were not significantly affected. Conclusions Our findings provide new insights into the effects of lithium on some drug transporters and drugmetabolizing enzymes in the BBB that may have consequences in pharmacotherapy.

Title

European Journal of Drug Metabolism and Pharmacokinetics

Publisher

Springer

Publisher Country

Germany

Indexing

Thomson Reuters

Impact Factor

1.68

Publication Type

Prtinted only

Volume

43

Year

2017

Pages

1-5