ArticleEuropean journal of drug metabolism and pharmacokinetics2017
Effect of Long-term In Vitro Lithium Exposure on mRNA Levels of Claudin-3, CYP1A1, ABCG2 and GSTM3 Genes in the hCMEC/D3 Human Brain Endothelial Cell Line.
Article in European journal of drug metabolism and pharmacokinetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 45 citations in OpenAlex.
- Ischemic stroke: molecular mechanisms of blood-brain barrier dysfunction and opportunities for drug development.Fluids and barriers of the CNS · 2026Review
- The neurobiological regulatory mechanism of brain edema.Frontiers in cellular neuroscience · 2026Review
- Relevance of red blood cell Lithium concentration in the management of Lithium-treated bipolar and unipolar disorders: a systematic narrative review.International journal of bipolar disorders · 2024Article
- Secretome of brain microvascular endothelial cells promotes endothelial barrier tightness and protects against hypoxia-induced vascular leakage.Molecular medicine (Cambridge, Mass.) · 2024Article
- Blood-brain barrier transporters: a translational consideration for CNS delivery of neurotherapeutics.Expert opinion on drug deliveryReview
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Authors and funding
6 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectivesLithium chloride (LiCl) has been shown to improve the tightness of brain endothelial cell monolayers in vitro by inhibition of the GSK-3β 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 drug-metabolizing 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.
methodsWe 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.
resultsOur 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.
conclusionsOur findings provide new insights into the effects of lithium on some drug transporters and drug-metabolizing enzymes in the BBB that may have consequences in pharmacotherapy.
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