Cannabidiol (CBD) Inhibited Rhodamine-123 Efflux in Cultured Vascular Endothelial Cells and Astrocytes Under Hypoxic Conditions

Despite the constant development of new antiepileptic drugs (AEDs), more than 30% of patients develop refractory epilepsy (RE) characterized by a multidrug-resistant (MDR) phenotype. The "transporters hypothesis" indicates that the mechanism of this MDR phenotype is the overexpression of A...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Auzmendi, Jerónimo, Palestro, Pablo Hernán, Blachman, Agustín, Gavernet, Luciana, Merelli, Amalia, Talevi, Alan, Calabrese, Graciela C., Ramos, Alberto Javier, Lazarowski, Alberto
Formato: Articulo
Lenguaje:Inglés
Publicado: 2020
Materias:
Ciencias Exactas
Biología
Cannabidiol
P-glycoprotein
hypoxia
endothelial cells
astrocytes
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/124846
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-124846
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Exactas
Biología
Cannabidiol
P-glycoprotein
hypoxia
endothelial cells
astrocytes
spellingShingle Ciencias Exactas
Biología
Cannabidiol
P-glycoprotein
hypoxia
endothelial cells
astrocytes
Auzmendi, Jerónimo
Palestro, Pablo Hernán
Blachman, Agustín
Gavernet, Luciana
Merelli, Amalia
Talevi, Alan
Calabrese, Graciela C.
Ramos, Alberto Javier
Lazarowski, Alberto
Cannabidiol (CBD) Inhibited Rhodamine-123 Efflux in Cultured Vascular Endothelial Cells and Astrocytes Under Hypoxic Conditions
topic_facet Ciencias Exactas
Biología
Cannabidiol
P-glycoprotein
hypoxia
endothelial cells
astrocytes
description Despite the constant development of new antiepileptic drugs (AEDs), more than 30% of patients develop refractory epilepsy (RE) characterized by a multidrug-resistant (MDR) phenotype. The "transporters hypothesis" indicates that the mechanism of this MDR phenotype is the overexpression of ABC transporters such as P-glycoprotein (P-gp) in the neurovascular unit cells, limiting access of the AEDs to the brain. Recent clinical trials and basic studies have shown encouraging results for the use of cannabinoids in RE, although its mechanisms of action are still not fully understood. Here, we have employed astrocytes and vascular endothelial cell cultures subjected to hypoxia, to test the effect of cannabidiol (CBD) on the P-gp-dependent Rhodamine-123 (Rho-123) efflux. Results show that during hypoxia, intracellular Rho-123 accumulation after CBD treatment is similar to that induced by the P-gp inhibitor Tariquidar (Tq). Noteworthy, this inhibition is like that registered in non-hypoxia conditions. Additionally, docking studies predicted that CBD could behave as a P-gp substrate by the interaction with several residues in the α-helix of the P-gp transmembrane domain. Overall, these findings suggest a direct effect of CBD on the Rho-123 P-gp-dependent efflux activity, which might explain why the CBD add-on treatment regimen in RE patients results in a significant reduction in seizure frequency.
format Articulo
Articulo
author Auzmendi, Jerónimo
Palestro, Pablo Hernán
Blachman, Agustín
Gavernet, Luciana
Merelli, Amalia
Talevi, Alan
Calabrese, Graciela C.
Ramos, Alberto Javier
Lazarowski, Alberto
author_facet Auzmendi, Jerónimo
Palestro, Pablo Hernán
Blachman, Agustín
Gavernet, Luciana
Merelli, Amalia
Talevi, Alan
Calabrese, Graciela C.
Ramos, Alberto Javier
Lazarowski, Alberto
author_sort Auzmendi, Jerónimo
title Cannabidiol (CBD) Inhibited Rhodamine-123 Efflux in Cultured Vascular Endothelial Cells and Astrocytes Under Hypoxic Conditions
title_short Cannabidiol (CBD) Inhibited Rhodamine-123 Efflux in Cultured Vascular Endothelial Cells and Astrocytes Under Hypoxic Conditions
title_full Cannabidiol (CBD) Inhibited Rhodamine-123 Efflux in Cultured Vascular Endothelial Cells and Astrocytes Under Hypoxic Conditions
title_fullStr Cannabidiol (CBD) Inhibited Rhodamine-123 Efflux in Cultured Vascular Endothelial Cells and Astrocytes Under Hypoxic Conditions
title_full_unstemmed Cannabidiol (CBD) Inhibited Rhodamine-123 Efflux in Cultured Vascular Endothelial Cells and Astrocytes Under Hypoxic Conditions
title_sort cannabidiol (cbd) inhibited rhodamine-123 efflux in cultured vascular endothelial cells and astrocytes under hypoxic conditions
publishDate 2020
url http://sedici.unlp.edu.ar/handle/10915/124846
work_keys_str_mv AT auzmendijeronimo cannabidiolcbdinhibitedrhodamine123effluxinculturedvascularendothelialcellsandastrocytesunderhypoxicconditions
AT palestropablohernan cannabidiolcbdinhibitedrhodamine123effluxinculturedvascularendothelialcellsandastrocytesunderhypoxicconditions
AT blachmanagustin cannabidiolcbdinhibitedrhodamine123effluxinculturedvascularendothelialcellsandastrocytesunderhypoxicconditions
AT gavernetluciana cannabidiolcbdinhibitedrhodamine123effluxinculturedvascularendothelialcellsandastrocytesunderhypoxicconditions
AT merelliamalia cannabidiolcbdinhibitedrhodamine123effluxinculturedvascularendothelialcellsandastrocytesunderhypoxicconditions
AT talevialan cannabidiolcbdinhibitedrhodamine123effluxinculturedvascularendothelialcellsandastrocytesunderhypoxicconditions
AT calabresegracielac cannabidiolcbdinhibitedrhodamine123effluxinculturedvascularendothelialcellsandastrocytesunderhypoxicconditions
AT ramosalbertojavier cannabidiolcbdinhibitedrhodamine123effluxinculturedvascularendothelialcellsandastrocytesunderhypoxicconditions
AT lazarowskialberto cannabidiolcbdinhibitedrhodamine123effluxinculturedvascularendothelialcellsandastrocytesunderhypoxicconditions
bdutipo_str Repositorios
_version_ 1764820451212656641

Ejemplares similares