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

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 re...

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Autores principales: Stoyanoff, Tania Romina, Todaro, Juan Santiago, Aguirre, María Victoria, Zimmermann, María Carla, Brandan, Nora Cristina
Formato: Artículo
Lenguaje:Inglés
Publicado: Elsevier Ireland Ltd 2022
Materias:
Sepsis
EPO induced renoprotection
Acceso en línea:http://repositorio.unne.edu.ar/handle/123456789/33813
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RIUNNE - Repositorio Institucional de la Universidad Nacional del Nordeste (UNNE) de Universidad Nacional del Nordeste
id I48-R184-123456789-33813
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spelling I48-R184-123456789-338132024-12-16T11:34:36Z Amelioration of lipopolysaccharide-induced acute kidney injury by erythropoietin : involvement of mitochondria-regulated apoptosis Stoyanoff, Tania Romina Todaro, Juan Santiago Aguirre, María Victoria Zimmermann, María Carla Brandan, Nora Cristina Sepsis EPO induced renoprotection 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 antiinflammatory, 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 24 h 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. 2022-04-08T19:03:43Z 2022-04-08T19:03:43Z 2014 Artículo Stoyanoff, Tania Romina, et al, 2014. Amelioration of lipopolysaccharide-induced acute kidney injury by erythropoietin : Involvement of mitochondria-regulated. Toxicology. Ámsterdam: Elsevier Ireland Ltd, vol. 318, p. 13-21. ISSN 0300-483X. http://repositorio.unne.edu.ar/handle/123456789/33813 eng openAccess http://creativecommons.org/licenses/by-nc-nd/2.5/ar/ application/pdf application/pdf Elsevier Ireland Ltd Toxicology, 2014, vol. 318, p. 13-21.
institution Universidad Nacional del Nordeste
institution_str I-48
repository_str R-184
collection RIUNNE - Repositorio Institucional de la Universidad Nacional del Nordeste (UNNE)
language Inglés
topic Sepsis
EPO induced renoprotection
spellingShingle Sepsis
EPO induced renoprotection
Stoyanoff, Tania Romina
Todaro, Juan Santiago
Aguirre, María Victoria
Zimmermann, María Carla
Brandan, Nora Cristina
Amelioration of lipopolysaccharide-induced acute kidney injury by erythropoietin : involvement of mitochondria-regulated apoptosis
topic_facet Sepsis
EPO induced renoprotection
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 antiinflammatory, 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 24 h 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.
format Artículo
author Stoyanoff, Tania Romina
Todaro, Juan Santiago
Aguirre, María Victoria
Zimmermann, María Carla
Brandan, Nora Cristina
author_facet Stoyanoff, Tania Romina
Todaro, Juan Santiago
Aguirre, María Victoria
Zimmermann, María Carla
Brandan, Nora Cristina
author_sort Stoyanoff, Tania Romina
title Amelioration of lipopolysaccharide-induced acute kidney injury by erythropoietin : involvement of mitochondria-regulated apoptosis
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
publisher Elsevier Ireland Ltd
publishDate 2022
url http://repositorio.unne.edu.ar/handle/123456789/33813
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