Progressive heart P-glycoprotein (P-gp) overexpression after experimental repetitive seizures (ERS) associated with fatal status epilepticus (FSE): Is it related with SUDEP?

Autores: Auzmendi, Jerónimo Andrés; Merelli, Amalia Margarita; Girardi, Elena Silvia; Orozco Suárez, Sandra; Rocha Arrieta, Luisa Lilia; Lazarowski, Alberto Jorge
Año de publicación: 2014
Idioma: inglés
Tipo de recurso: artículo
Estado: versión publicada
Descripción: Patients with refractory epilepsy (RE) have increased risk of Sudden Unexpected Death in Epilepsy (SUDEP), where acute and fatal heart failure is suspected. High seizure frequency, polypharmacy, changes in dosing, persistent low AED levels or poor adherence to therapy are the greatest risk factors of SUDEP and are also features observed in RE. We evaluated the progressive P-gp overexpression in heart, related with the development of fatal status epilepticus (FSE) after experimental repetitive seizures (ERS). Male Wistar rats (180–230g) were daily injected (i.p) with Pentylenetetrazole (PTZ; 45mg/kg; n=18) or saline (Controls; n=6). Severity of seizures was recorded. Four PTZ-treated rats were sacrificed at 4th-7th day respectively. Ten remaining rats, underwent same treatment until develop fatal status epilepticus (FSE). Brains and hearts were studied by immunofluorecent method for P-glycoptrotein (P-gp) expression. Seizures were observed each day of PTZ treatment, associated with a progressive P-gp overexpression in heart and FSE at 9th day. Using the same PTZ model, we previously demonstrated that progressive brain P-gp overexpression contributes to cell membrane depolarization of hippocampus and neocortex. These are the first evidences showing that ERS induces a simultaneous and progressive P-gp overexpression in brain and heart associated with FSE, and suggests a role for this pattern expression of P-gp as risk factor for death during SE. The simultaneous and spontaneous death of all animals during SE observed only at day 9th, suggest that a higher P-gp overexpression in cardiomyocytes could play a role in SUDEP, however, because it is only a study descriptive, further researches are needed to confirm this hypothesis.
Fil: Auzmendi, Jerónimo Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Merelli, Amalia Margarita. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Girardi, Elena Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Orozco Suárez, Sandra. Centro Médico Nacional Siglo XXI; México
Fil: Rocha Arrieta, Luisa Lilia. Centro de Investigación y de Estudios Avanzados. Departamento de Farmacobiología; México
Fil: Lazarowski, Alberto Jorge. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Fundación Investigar; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Materia: P-GLYCOPROTEIN
REPETITIVE SEIZURES
PENTYLENETETRAZOL
SUDEP
STATUS EPILEPTICUS
MYOCARDIUM
Nivel de accesibilidad: acceso abierto
Condiciones de uso: https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
Institución: Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador: oai:ri.conicet.gov.ar:11336/17282

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spelling	Progressive heart P-glycoprotein (P-gp) overexpression after experimental repetitive seizures (ERS) associated with fatal status epilepticus (FSE): Is it related with SUDEP?Auzmendi, Jerónimo AndrésMerelli, Amalia MargaritaGirardi, Elena SilviaOrozco Suárez, SandraRocha Arrieta, Luisa LiliaLazarowski, Alberto JorgeP-GLYCOPROTEINREPETITIVE SEIZURESPENTYLENETETRAZOLSUDEPSTATUS EPILEPTICUSMYOCARDIUMhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Patients with refractory epilepsy (RE) have increased risk of Sudden Unexpected Death in Epilepsy (SUDEP), where acute and fatal heart failure is suspected. High seizure frequency, polypharmacy, changes in dosing, persistent low AED levels or poor adherence to therapy are the greatest risk factors of SUDEP and are also features observed in RE. We evaluated the progressive P-gp overexpression in heart, related with the development of fatal status epilepticus (FSE) after experimental repetitive seizures (ERS). Male Wistar rats (180–230g) were daily injected (i.p) with Pentylenetetrazole (PTZ; 45mg/kg; n=18) or saline (Controls; n=6). Severity of seizures was recorded. Four PTZ-treated rats were sacrificed at 4th-7th day respectively. Ten remaining rats, underwent same treatment until develop fatal status epilepticus (FSE). Brains and hearts were studied by immunofluorecent method for P-glycoptrotein (P-gp) expression. Seizures were observed each day of PTZ treatment, associated with a progressive P-gp overexpression in heart and FSE at 9th day. Using the same PTZ model, we previously demonstrated that progressive brain P-gp overexpression contributes to cell membrane depolarization of hippocampus and neocortex. These are the first evidences showing that ERS induces a simultaneous and progressive P-gp overexpression in brain and heart associated with FSE, and suggests a role for this pattern expression of P-gp as risk factor for death during SE. The simultaneous and spontaneous death of all animals during SE observed only at day 9th, suggest that a higher P-gp overexpression in cardiomyocytes could play a role in SUDEP, however, because it is only a study descriptive, further researches are needed to confirm this hypothesis.Fil: Auzmendi, Jerónimo Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Merelli, Amalia Margarita. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Girardi, Elena Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Orozco Suárez, Sandra. Centro Médico Nacional Siglo XXI; MéxicoFil: Rocha Arrieta, Luisa Lilia. Centro de Investigación y de Estudios Avanzados. Departamento de Farmacobiología; MéxicoFil: Lazarowski, Alberto Jorge. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Fundación Investigar; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaSmart Science & Technology2014-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/17282Auzmendi, Jerónimo Andrés; Merelli, Amalia Margarita; Girardi, Elena Silvia; Orozco Suárez, Sandra; Rocha Arrieta, Luisa Lilia; et al.; Progressive heart P-glycoprotein (P-gp) overexpression after experimental repetitive seizures (ERS) associated with fatal status epilepticus (FSE): Is it related with SUDEP?; Smart Science & Technology; Molecular & Cellular Epilepsy; 1; 2-2014; 1-92330-3891enginfo:eu-repo/semantics/altIdentifier/url/http://www.smartscitech.com/index.php/MCE/article/view/66info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:10:50Zoai:ri.conicet.gov.ar:11336/17282instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:10:50.414CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv	Progressive heart P-glycoprotein (P-gp) overexpression after experimental repetitive seizures (ERS) associated with fatal status epilepticus (FSE): Is it related with SUDEP?
title	Progressive heart P-glycoprotein (P-gp) overexpression after experimental repetitive seizures (ERS) associated with fatal status epilepticus (FSE): Is it related with SUDEP?
spellingShingle	Progressive heart P-glycoprotein (P-gp) overexpression after experimental repetitive seizures (ERS) associated with fatal status epilepticus (FSE): Is it related with SUDEP? Auzmendi, Jerónimo Andrés P-GLYCOPROTEIN REPETITIVE SEIZURES PENTYLENETETRAZOL SUDEP STATUS EPILEPTICUS MYOCARDIUM
title_short	Progressive heart P-glycoprotein (P-gp) overexpression after experimental repetitive seizures (ERS) associated with fatal status epilepticus (FSE): Is it related with SUDEP?
title_full	Progressive heart P-glycoprotein (P-gp) overexpression after experimental repetitive seizures (ERS) associated with fatal status epilepticus (FSE): Is it related with SUDEP?
title_fullStr	Progressive heart P-glycoprotein (P-gp) overexpression after experimental repetitive seizures (ERS) associated with fatal status epilepticus (FSE): Is it related with SUDEP?
title_full_unstemmed	Progressive heart P-glycoprotein (P-gp) overexpression after experimental repetitive seizures (ERS) associated with fatal status epilepticus (FSE): Is it related with SUDEP?
title_sort	Progressive heart P-glycoprotein (P-gp) overexpression after experimental repetitive seizures (ERS) associated with fatal status epilepticus (FSE): Is it related with SUDEP?
dc.creator.none.fl_str_mv	Auzmendi, Jerónimo Andrés Merelli, Amalia Margarita Girardi, Elena Silvia Orozco Suárez, Sandra Rocha Arrieta, Luisa Lilia Lazarowski, Alberto Jorge
author	Auzmendi, Jerónimo Andrés
author_facet	Auzmendi, Jerónimo Andrés Merelli, Amalia Margarita Girardi, Elena Silvia Orozco Suárez, Sandra Rocha Arrieta, Luisa Lilia Lazarowski, Alberto Jorge
author_role	author
author2	Merelli, Amalia Margarita Girardi, Elena Silvia Orozco Suárez, Sandra Rocha Arrieta, Luisa Lilia Lazarowski, Alberto Jorge
author2_role	author author author author author
dc.subject.none.fl_str_mv	P-GLYCOPROTEIN REPETITIVE SEIZURES PENTYLENETETRAZOL SUDEP STATUS EPILEPTICUS MYOCARDIUM
topic	P-GLYCOPROTEIN REPETITIVE SEIZURES PENTYLENETETRAZOL SUDEP STATUS EPILEPTICUS MYOCARDIUM
purl_subject.fl_str_mv	https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv	Patients with refractory epilepsy (RE) have increased risk of Sudden Unexpected Death in Epilepsy (SUDEP), where acute and fatal heart failure is suspected. High seizure frequency, polypharmacy, changes in dosing, persistent low AED levels or poor adherence to therapy are the greatest risk factors of SUDEP and are also features observed in RE. We evaluated the progressive P-gp overexpression in heart, related with the development of fatal status epilepticus (FSE) after experimental repetitive seizures (ERS). Male Wistar rats (180–230g) were daily injected (i.p) with Pentylenetetrazole (PTZ; 45mg/kg; n=18) or saline (Controls; n=6). Severity of seizures was recorded. Four PTZ-treated rats were sacrificed at 4th-7th day respectively. Ten remaining rats, underwent same treatment until develop fatal status epilepticus (FSE). Brains and hearts were studied by immunofluorecent method for P-glycoptrotein (P-gp) expression. Seizures were observed each day of PTZ treatment, associated with a progressive P-gp overexpression in heart and FSE at 9th day. Using the same PTZ model, we previously demonstrated that progressive brain P-gp overexpression contributes to cell membrane depolarization of hippocampus and neocortex. These are the first evidences showing that ERS induces a simultaneous and progressive P-gp overexpression in brain and heart associated with FSE, and suggests a role for this pattern expression of P-gp as risk factor for death during SE. The simultaneous and spontaneous death of all animals during SE observed only at day 9th, suggest that a higher P-gp overexpression in cardiomyocytes could play a role in SUDEP, however, because it is only a study descriptive, further researches are needed to confirm this hypothesis. Fil: Auzmendi, Jerónimo Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina Fil: Merelli, Amalia Margarita. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina Fil: Girardi, Elena Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina Fil: Orozco Suárez, Sandra. Centro Médico Nacional Siglo XXI; México Fil: Rocha Arrieta, Luisa Lilia. Centro de Investigación y de Estudios Avanzados. Departamento de Farmacobiología; México Fil: Lazarowski, Alberto Jorge. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Fundación Investigar; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
description	Patients with refractory epilepsy (RE) have increased risk of Sudden Unexpected Death in Epilepsy (SUDEP), where acute and fatal heart failure is suspected. High seizure frequency, polypharmacy, changes in dosing, persistent low AED levels or poor adherence to therapy are the greatest risk factors of SUDEP and are also features observed in RE. We evaluated the progressive P-gp overexpression in heart, related with the development of fatal status epilepticus (FSE) after experimental repetitive seizures (ERS). Male Wistar rats (180–230g) were daily injected (i.p) with Pentylenetetrazole (PTZ; 45mg/kg; n=18) or saline (Controls; n=6). Severity of seizures was recorded. Four PTZ-treated rats were sacrificed at 4th-7th day respectively. Ten remaining rats, underwent same treatment until develop fatal status epilepticus (FSE). Brains and hearts were studied by immunofluorecent method for P-glycoptrotein (P-gp) expression. Seizures were observed each day of PTZ treatment, associated with a progressive P-gp overexpression in heart and FSE at 9th day. Using the same PTZ model, we previously demonstrated that progressive brain P-gp overexpression contributes to cell membrane depolarization of hippocampus and neocortex. These are the first evidences showing that ERS induces a simultaneous and progressive P-gp overexpression in brain and heart associated with FSE, and suggests a role for this pattern expression of P-gp as risk factor for death during SE. The simultaneous and spontaneous death of all animals during SE observed only at day 9th, suggest that a higher P-gp overexpression in cardiomyocytes could play a role in SUDEP, however, because it is only a study descriptive, further researches are needed to confirm this hypothesis.
publishDate	2014
dc.date.none.fl_str_mv	2014-02
dc.type.none.fl_str_mv	info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo
format	article
status_str	publishedVersion
dc.identifier.none.fl_str_mv	http://hdl.handle.net/11336/17282 Auzmendi, Jerónimo Andrés; Merelli, Amalia Margarita; Girardi, Elena Silvia; Orozco Suárez, Sandra; Rocha Arrieta, Luisa Lilia; et al.; Progressive heart P-glycoprotein (P-gp) overexpression after experimental repetitive seizures (ERS) associated with fatal status epilepticus (FSE): Is it related with SUDEP?; Smart Science & Technology; Molecular & Cellular Epilepsy; 1; 2-2014; 1-9 2330-3891
url	http://hdl.handle.net/11336/17282
identifier_str_mv	Auzmendi, Jerónimo Andrés; Merelli, Amalia Margarita; Girardi, Elena Silvia; Orozco Suárez, Sandra; Rocha Arrieta, Luisa Lilia; et al.; Progressive heart P-glycoprotein (P-gp) overexpression after experimental repetitive seizures (ERS) associated with fatal status epilepticus (FSE): Is it related with SUDEP?; Smart Science & Technology; Molecular & Cellular Epilepsy; 1; 2-2014; 1-9 2330-3891
dc.language.none.fl_str_mv	eng
language	eng
dc.relation.none.fl_str_mv	info:eu-repo/semantics/altIdentifier/url/http://www.smartscitech.com/index.php/MCE/article/view/66
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dc.publisher.none.fl_str_mv	Smart Science & Technology
publisher.none.fl_str_mv	Smart Science & Technology
dc.source.none.fl_str_mv	reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas
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instname_str	Consejo Nacional de Investigaciones Científicas y Técnicas
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repository.mail.fl_str_mv	dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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Progressive heart P-glycoprotein (P-gp) overexpression after experimental repetitive seizures (ERS) associated with fatal status epilepticus (FSE): Is it related with SUDEP?

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