ArticlePharmaceutical research2014
Marked differences in the effect of antiepileptic and cytostatic drugs on the functionality of P-glycoprotein in human and rat brain capillary endothelial cell lines.
Article in Pharmaceutical research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
13 citing papers in PubMed, 31 citations in OpenAlex.
- Effect of Apolipoprotein E isoforms on the Abundance and Function of P-glycoprotein in Human Brain Microvascular Endothelial Cells.Pharmaceutical research · 2024Article
- Similarities and differences in the localization, trafficking, and function of P-glycoprotein in MDR1-EGFP-transduced rat versus human brain capillary endothelial cell lines.Fluids and barriers of the CNS · 2021Article
- Oligodendroglioma: A Review of Management and Pathways.Frontiers in molecular neuroscience · 2021Review
- Entry of antiepileptic drugs (valproate and lamotrigine) into the developing rat brain.F1000Research · 2021Article
- Heat Shock Proteins Accelerate the Maturation of Brain Endothelial Cell Glucocorticoid Receptor in Focal Human Drug-Resistant Epilepsy.Molecular neurobiology · 2020Article
- Novel Intrinsic Mechanisms of Active Drug Extrusion at the Blood-Brain Barrier: Potential Targets for Enhancing Drug Delivery to the Brain?Pharmaceutics · 2020Review
- A face-to-face comparison of claudin-5 transduced human brain endothelial (hCMEC/D3) cells with porcine brain endothelial cells as blood-brain barrier models for drug transport studies.Fluids and barriers of the CNS · 2020Article
- Investigating Maternal Brain Alterations in Preeclampsia: the Need for a Multidisciplinary Effort.Current hypertension reports · 2019Review
- In Vitro Assessment of the Effect of Antiepileptic Drugs on Expression and Function of ABC Transporters and Their Interactions with ABCC2.Molecules (Basel, Switzerland) · 2017Article
- SLC and ABC Transporters: Expression, Localization, and Species Differences at the Blood-Brain and the Blood-Cerebrospinal Fluid Barriers.The AAPS journal · 2017Review
- Inhibition of mTOR Pathway by Rapamycin Decreases P-glycoprotein Expression and Spontaneous Seizures in Pharmacoresistant Epilepsy.Journal of molecular neuroscience : MN · 2017Article
- Intercellular transfer of P-glycoprotein in human blood-brain barrier endothelial cells is increased by histone deacetylase inhibitors.Scientific reports · 2016Article
- Seizures in oligodendroglial tumors.CNS oncology · 2015Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeThe expression of P-glycoprotein (Pgp) is increased in brain capillary endothelial cells (BCECs) of patients with pharmacoresistant epilepsy. This may restrict the penetration of antiepileptic drugs (AEDs) into the brain. However, the mechanisms underlying increased Pgp expression in epilepsy patients are not known. One possibility is that AEDs induce the expression and functionality of Pgp in BCECs. Several older AEDs that induce human cytochrome P450 enzymes also induce Pgp in hepatocytes and enterocytes, but whether this extends to Pgp at the human BBB and to newer AEDs is not known.
methodsThis prompted us to study the effects of various old and new AEDs on Pgp functionality in the human BCEC line, hCMEC/D3, using the rhodamine 123 (Rho123) efflux assay. For comparison, experiments were performed in two rat BCEC lines, RBE4 and GPNT, and primary cultures of rat and pig BCECs. Furthermore, known Pgp inducers, such as dexamethasone and several cytostatic drugs, were included in our experiments.
resultsUnder control conditions, GPNT cells exhibited the highest and RBE4 the lowest Pgp expression and Rho123 efflux, while intermediate values were determined in hCMEC/D3. Known Pgp inducers increased Rho123 efflux in all cell lines, but marked inter-cell line differences in effect size were observed. Of the various AEDs examined, only carbamazepine (100 μM) moderately increased Pgp functionality in hCMEC/D3, while valproate (300 μM) inhibited Pgp.
conclusionsThese data do not indicate that treatment with AEDs causes a clinically relevant induction in Pgp functionality in BCECs that form the BBB.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.