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dc.contributor.author
Auzmendi, Jerónimo Andrés
dc.contributor.author
Orozco Suárez, Sandra
dc.contributor.author
Bañuelos Cabrera, Ivette
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González Trujano, Maria Eva
dc.contributor.author
Calixto Gonzàlez, Eduardo
dc.contributor.author
Rocha, Luis
dc.contributor.author
Lazarowski, Alberto
dc.date.available
2016-11-17T14:29:00Z
dc.date.issued
2013-03
dc.identifier.citation
Auzmendi, Jerónimo Andrés; Orozco Suárez, Sandra; Bañuelos Cabrera, Ivette; González Trujano, Maria Eva; Calixto Gonzàlez, Eduardo; et al.; P-Glycoprotein contributes to cell membrane depolarization of hippocampus and neocortex in a model of repetitive seizures induced by pentylenetetrazole in rats; Bentham Science Publishers; Current Pharmaceutical Design.; 19; 38; 3-2013; 6732-6738
dc.identifier.issn
1381-6128
dc.identifier.uri
http://hdl.handle.net/11336/8282
dc.description.abstract
P-glycoprotein (P-gp) has been associated with pharmacoresistance and mechanisms regulating the membrane potential. However, at present it is unknown if P-gp overexpression in brain is associated with changes in membrane depolarization in refractory epilepsy. Experiments were designed to evaluate the membrane depolarization and P-gp overexpression induced by repetitive pentilenetetrazole (PTZ)-induced-seizures. Wistar rats were daily treated with PTZ during 4 to 7 days (PTZ4 and PTZ7 groups), and the brain was used to evaluate membrane potential by in vitro electrophysiological procedures and using bis-oxonol dye, [bis-(1,3-dibutylbarbituric acid) trimethine oxonol (DiBAC4(3)], a fluorescence dye voltage-sensitive to membrane potentials. Rats with repetitive PTZ-induced seizures demonstrated lower phenytoin-induced anticonvulsant effects, increased number of DiBAC4(3) fluorescence cells and P-gp overexpression in hippocampus and neocortex, as well as augmentation of the induced fEPSP in CA1 field. These changes were more evident in PTZ7 group. Phenytoin or phenytoin plus nimodipine (a P-gp antagonist) avoided the enhanced fEPSP and decreased DiBAC4(3) fluorescence in animals from PTZ4 group. However, in PTZ7 group these effects were evident only when phenytoin was combined with nimodipine. An additional flow cytometry study demonstrated increased intracellular accumulation of DiBAC4(3) in K562 leukemic cells that overexpress MDR-1 and COX-2 genes, and are refractory to specific cytotoxic agents. These results represent the first evidence supporting the notion that brain P-gp overexpression contributes to a progressive seizure-related membranes depolarization in hippocampus and neocortex. Further experiments should be carried out to confirm the role of P-gp on membrane depolarization and epileptogenesis process.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Bentham Science Publishers
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
P-Glicoprotein
dc.subject
Membrane Depolarization
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Ptz
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Refractory Epilepsy
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Epileptogenesis
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Otras Ciencias de la Salud
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Ciencias de la Salud
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
P-Glycoprotein contributes to cell membrane depolarization of hippocampus and neocortex in a model of repetitive seizures induced by pentylenetetrazole in rats
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2016-10-25T19:27:25Z
dc.journal.volume
19
dc.journal.number
38
dc.journal.pagination
6732-6738
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Oak Park
dc.description.fil
Fil: Auzmendi, Jerónimo Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencias "Profesor Eduardo de Robertis"; Argentina
dc.description.fil
Fil: Orozco Suárez, Sandra. Centro Medico Nacional Siglo XXI; México
dc.description.fil
Fil: Bañuelos Cabrera, Ivette. Centro de Investigación y de Estudios Avanzados, Sede Sur; México
dc.description.fil
Fil: González Trujano, Maria Eva. Instituto Nacional de Psiquiatría “Ramón de la Fuente”; México
dc.description.fil
Fil: Calixto Gonzàlez, Eduardo. Instituto Nacional de Psiquiatría “Ramón de la Fuente”; México
dc.description.fil
Fil: Rocha, Luis. Centro de Investigación y Estudios Avanzados, Sede Sur; México
dc.description.fil
Fil: Lazarowski, Alberto. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencias "Profesor Eduardo de Robertis"; Argentina
dc.journal.title
Current Pharmaceutical Design.
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.2174/1381612811319380006
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.eurekaselect.com/116871/article
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