Amelioration of lipopolysaccharide-induced acute kidney injury by erythropoietin: involvement of mitochondria-regulated apoptosis

Autores
Stoyanoff, Tania Romina; Todaro, Juan Santiago; Aguirre, María Victoria; Zimmermann, Maria Carla; Brandan, Nora Cristina
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Sepsis remains the most important cause of acute kidney injury (AKI) in critically ill patients and is an independent predictor of poor outcome. The administration of lipopolysaccharide (LPS) to animals reproduces most of the clinical features of sepsis, including AKI, a condition associated with renal cellular dysfunction and apoptosis. Erythropoietin (EPO) is a well known cytoprotective multifunctional hormone, which exerts anti-inflammatory, anti-oxidant, anti-apoptotic and angiogenic effects in several tissues. The aim of this study was to evaluate the underlying mechanisms of EPO renoprotection through the expression of the EPO receptor (EPO-R) and the modulation of the intrinsic apoptotic pathway in LPS-induced AKI. Male inbred Balb/c mice were divided in four experimental groups: Control, LPS (8 mg/kg i.p.), EPO (3000 IU sc) and LPS+EPO. Assessment of renal function, histological examination, TUNEL in situ assay, immunohistochemistry and Western blottings of caspase-3, Bax, Bcl-xL, EPO-R and Cytochrome c were performed at 24h post treatment. LPS+EPO treatment significantly improved renal function and ameliorated histopathological injury when compared to the LPS treated group. Results showed that EPO treatment attenuates renal tubular apoptosis through: (a) the overexpression of EPO-R in tubular interstitial cells, (b) the reduction of Bax/Bcl-xL ratio, (c) the inhibition Cytochrome c release into the cytosol and (d) the decrease of the active caspase-3 expression. This study suggests that EPO exerts renoprotection on an experimental model of LPS-induced AKI. EPO induced renoprotection involves an anti-apoptotic effect through the expression of EPO-R and the regulation of the mitochondrial apoptotic pathway
Fil: Stoyanoff, Tania Romina. Universidad Nacional del Nordeste. Facultad de Medicina. Cátedra de Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Todaro, Juan Santiago. Universidad Nacional del Nordeste. Facultad de Medicina. Cátedra de Bioquímica; Argentina
Fil: Aguirre, María Victoria. Universidad Nacional del Nordeste. Facultad de Medicina. Cátedra de Bioquímica; Argentina
Fil: Zimmermann, Maria Carla. Universidad Nacional del Nordeste. Facultad de Medicina. Cátedra de Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Brandan, Nora Cristina. Universidad Nacional del Nordeste. Facultad de Medicina. Cátedra de Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
Acute Kidney Injury
Erythropoietin
Renoprotection
Epo Rh Treatment
Lps-Induced Aki
Apoptosis
Cytochrome C
Epo-R
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/27606
Acceder
id CONICETDig_4323114f30cdaea0fd2cfa3f49a57d14
oai_identifier_str oai:ri.conicet.gov.ar:11336/27606
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Amelioration of lipopolysaccharide-induced acute kidney injury by erythropoietin: involvement of mitochondria-regulated apoptosisStoyanoff, Tania RominaTodaro, Juan SantiagoAguirre, María VictoriaZimmermann, Maria CarlaBrandan, Nora CristinaAcute Kidney InjuryErythropoietinRenoprotectionEpo Rh TreatmentLps-Induced AkiApoptosisCytochrome CEpo-Rhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Sepsis remains the most important cause of acute kidney injury (AKI) in critically ill patients and is an independent predictor of poor outcome. The administration of lipopolysaccharide (LPS) to animals reproduces most of the clinical features of sepsis, including AKI, a condition associated with renal cellular dysfunction and apoptosis. Erythropoietin (EPO) is a well known cytoprotective multifunctional hormone, which exerts anti-inflammatory, anti-oxidant, anti-apoptotic and angiogenic effects in several tissues. The aim of this study was to evaluate the underlying mechanisms of EPO renoprotection through the expression of the EPO receptor (EPO-R) and the modulation of the intrinsic apoptotic pathway in LPS-induced AKI. Male inbred Balb/c mice were divided in four experimental groups: Control, LPS (8 mg/kg i.p.), EPO (3000 IU sc) and LPS+EPO. Assessment of renal function, histological examination, TUNEL in situ assay, immunohistochemistry and Western blottings of caspase-3, Bax, Bcl-xL, EPO-R and Cytochrome c were performed at 24h post treatment. LPS+EPO treatment significantly improved renal function and ameliorated histopathological injury when compared to the LPS treated group. Results showed that EPO treatment attenuates renal tubular apoptosis through: (a) the overexpression of EPO-R in tubular interstitial cells, (b) the reduction of Bax/Bcl-xL ratio, (c) the inhibition Cytochrome c release into the cytosol and (d) the decrease of the active caspase-3 expression. This study suggests that EPO exerts renoprotection on an experimental model of LPS-induced AKI. EPO induced renoprotection involves an anti-apoptotic effect through the expression of EPO-R and the regulation of the mitochondrial apoptotic pathwayFil: Stoyanoff, Tania Romina. Universidad Nacional del Nordeste. Facultad de Medicina. Cátedra de Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Todaro, Juan Santiago. Universidad Nacional del Nordeste. Facultad de Medicina. Cátedra de Bioquímica; ArgentinaFil: Aguirre, María Victoria. Universidad Nacional del Nordeste. Facultad de Medicina. Cátedra de Bioquímica; ArgentinaFil: Zimmermann, Maria Carla. Universidad Nacional del Nordeste. Facultad de Medicina. Cátedra de Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Brandan, Nora Cristina. Universidad Nacional del Nordeste. Facultad de Medicina. Cátedra de Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaElsevier Ireland2014-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/27606Stoyanoff, Tania Romina; Todaro, Juan Santiago; Aguirre, María Victoria; Zimmermann, Maria Carla; Brandan, Nora Cristina; Amelioration of lipopolysaccharide-induced acute kidney injury by erythropoietin: involvement of mitochondria-regulated apoptosis; Elsevier Ireland; Toxicology; 318; 2-2014; 13-210300-483X1879-3185CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.tox.2014.01.011info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0300483X14000237info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:32:48Zoai:ri.conicet.gov.ar:11336/27606instacron: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 10:32:48.59CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Amelioration of lipopolysaccharide-induced acute kidney injury by erythropoietin: involvement of mitochondria-regulated apoptosis
title Amelioration of lipopolysaccharide-induced acute kidney injury by erythropoietin: involvement of mitochondria-regulated apoptosis
spellingShingle Amelioration of lipopolysaccharide-induced acute kidney injury by erythropoietin: involvement of mitochondria-regulated apoptosis
Stoyanoff, Tania Romina
Acute Kidney Injury
Erythropoietin
Renoprotection
Epo Rh Treatment
Lps-Induced Aki
Apoptosis
Cytochrome C
Epo-R
title_short Amelioration of lipopolysaccharide-induced acute kidney injury by erythropoietin: involvement of mitochondria-regulated apoptosis
title_full Amelioration of lipopolysaccharide-induced acute kidney injury by erythropoietin: involvement of mitochondria-regulated apoptosis
title_fullStr Amelioration of lipopolysaccharide-induced acute kidney injury by erythropoietin: involvement of mitochondria-regulated apoptosis
title_full_unstemmed Amelioration of lipopolysaccharide-induced acute kidney injury by erythropoietin: involvement of mitochondria-regulated apoptosis
title_sort Amelioration of lipopolysaccharide-induced acute kidney injury by erythropoietin: involvement of mitochondria-regulated apoptosis
dc.creator.none.fl_str_mv Stoyanoff, Tania Romina
Todaro, Juan Santiago
Aguirre, María Victoria
Zimmermann, Maria Carla
Brandan, Nora Cristina
author Stoyanoff, Tania Romina
author_facet Stoyanoff, Tania Romina
Todaro, Juan Santiago
Aguirre, María Victoria
Zimmermann, Maria Carla
Brandan, Nora Cristina
author_role author
author2 Todaro, Juan Santiago
Aguirre, María Victoria
Zimmermann, Maria Carla
Brandan, Nora Cristina
author2_role author
author
author
author
dc.subject.none.fl_str_mv Acute Kidney Injury
Erythropoietin
Renoprotection
Epo Rh Treatment
Lps-Induced Aki
Apoptosis
Cytochrome C
Epo-R
topic Acute Kidney Injury
Erythropoietin
Renoprotection
Epo Rh Treatment
Lps-Induced Aki
Apoptosis
Cytochrome C
Epo-R
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Sepsis remains the most important cause of acute kidney injury (AKI) in critically ill patients and is an independent predictor of poor outcome. The administration of lipopolysaccharide (LPS) to animals reproduces most of the clinical features of sepsis, including AKI, a condition associated with renal cellular dysfunction and apoptosis. Erythropoietin (EPO) is a well known cytoprotective multifunctional hormone, which exerts anti-inflammatory, anti-oxidant, anti-apoptotic and angiogenic effects in several tissues. The aim of this study was to evaluate the underlying mechanisms of EPO renoprotection through the expression of the EPO receptor (EPO-R) and the modulation of the intrinsic apoptotic pathway in LPS-induced AKI. Male inbred Balb/c mice were divided in four experimental groups: Control, LPS (8 mg/kg i.p.), EPO (3000 IU sc) and LPS+EPO. Assessment of renal function, histological examination, TUNEL in situ assay, immunohistochemistry and Western blottings of caspase-3, Bax, Bcl-xL, EPO-R and Cytochrome c were performed at 24h post treatment. LPS+EPO treatment significantly improved renal function and ameliorated histopathological injury when compared to the LPS treated group. Results showed that EPO treatment attenuates renal tubular apoptosis through: (a) the overexpression of EPO-R in tubular interstitial cells, (b) the reduction of Bax/Bcl-xL ratio, (c) the inhibition Cytochrome c release into the cytosol and (d) the decrease of the active caspase-3 expression. This study suggests that EPO exerts renoprotection on an experimental model of LPS-induced AKI. EPO induced renoprotection involves an anti-apoptotic effect through the expression of EPO-R and the regulation of the mitochondrial apoptotic pathway
Fil: Stoyanoff, Tania Romina. Universidad Nacional del Nordeste. Facultad de Medicina. Cátedra de Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Todaro, Juan Santiago. Universidad Nacional del Nordeste. Facultad de Medicina. Cátedra de Bioquímica; Argentina
Fil: Aguirre, María Victoria. Universidad Nacional del Nordeste. Facultad de Medicina. Cátedra de Bioquímica; Argentina
Fil: Zimmermann, Maria Carla. Universidad Nacional del Nordeste. Facultad de Medicina. Cátedra de Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Brandan, Nora Cristina. Universidad Nacional del Nordeste. Facultad de Medicina. Cátedra de Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Sepsis remains the most important cause of acute kidney injury (AKI) in critically ill patients and is an independent predictor of poor outcome. The administration of lipopolysaccharide (LPS) to animals reproduces most of the clinical features of sepsis, including AKI, a condition associated with renal cellular dysfunction and apoptosis. Erythropoietin (EPO) is a well known cytoprotective multifunctional hormone, which exerts anti-inflammatory, anti-oxidant, anti-apoptotic and angiogenic effects in several tissues. The aim of this study was to evaluate the underlying mechanisms of EPO renoprotection through the expression of the EPO receptor (EPO-R) and the modulation of the intrinsic apoptotic pathway in LPS-induced AKI. Male inbred Balb/c mice were divided in four experimental groups: Control, LPS (8 mg/kg i.p.), EPO (3000 IU sc) and LPS+EPO. Assessment of renal function, histological examination, TUNEL in situ assay, immunohistochemistry and Western blottings of caspase-3, Bax, Bcl-xL, EPO-R and Cytochrome c were performed at 24h post treatment. LPS+EPO treatment significantly improved renal function and ameliorated histopathological injury when compared to the LPS treated group. Results showed that EPO treatment attenuates renal tubular apoptosis through: (a) the overexpression of EPO-R in tubular interstitial cells, (b) the reduction of Bax/Bcl-xL ratio, (c) the inhibition Cytochrome c release into the cytosol and (d) the decrease of the active caspase-3 expression. This study suggests that EPO exerts renoprotection on an experimental model of LPS-induced AKI. EPO induced renoprotection involves an anti-apoptotic effect through the expression of EPO-R and the regulation of the mitochondrial apoptotic pathway
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/11336/27606
Stoyanoff, Tania Romina; Todaro, Juan Santiago; Aguirre, María Victoria; Zimmermann, Maria Carla; Brandan, Nora Cristina; Amelioration of lipopolysaccharide-induced acute kidney injury by erythropoietin: involvement of mitochondria-regulated apoptosis; Elsevier Ireland; Toxicology; 318; 2-2014; 13-21
0300-483X
1879-3185
CONICET Digital
CONICET
url http://hdl.handle.net/11336/27606
identifier_str_mv Stoyanoff, Tania Romina; Todaro, Juan Santiago; Aguirre, María Victoria; Zimmermann, Maria Carla; Brandan, Nora Cristina; Amelioration of lipopolysaccharide-induced acute kidney injury by erythropoietin: involvement of mitochondria-regulated apoptosis; Elsevier Ireland; Toxicology; 318; 2-2014; 13-21
0300-483X
1879-3185
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.tox.2014.01.011
info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0300483X14000237
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Ireland
publisher.none.fl_str_mv Elsevier Ireland
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1844614342591381504
score 13.070432

Publicaciones similares