Erythropoietin attenuates LPS-induced microvascular damage in a murine model of septic acute kidney injury

Acute kidney injury (AKI) is a frequent complication of sepsis, with a high mortality. Hallmarks of septic-AKI include inflammation, endothelial injury, and tissue hypoxia. Therefore, it would be of interest to develop therapeutic approaches for improving the microvascular damage in septic-AKI....

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Autores principales: Stoyanoff, Tania Romina, Rodríguez, Juan Pablo, Todaro, Juan Santiago, Melana Colavita, Juan Pablo, Torres, Adriana Mónica, Aguirre, María Victoria
Formato: Artículo
Lenguaje:Inglés
Publicado: France-editions Scientifiques Medicales Elsevier 2021
Materias:
Septic AKI
Erythropoietin
Hypoxia
Microvascular injury
Acceso en línea:http://repositorio.unne.edu.ar/handle/123456789/28093
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RIUNNE - Repositorio Institucional de la Universidad Nacional del Nordeste (UNNE) de Universidad Nacional del Nordeste
id I48-R184-123456789-28093
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spelling I48-R184-123456789-280932025-03-06T11:08:11Z Erythropoietin attenuates LPS-induced microvascular damage in a murine model of septic acute kidney injury Stoyanoff, Tania Romina Rodríguez, Juan Pablo Todaro, Juan Santiago Melana Colavita, Juan Pablo Torres, Adriana Mónica Aguirre, María Victoria Septic AKI Erythropoietin Hypoxia Microvascular injury Acute kidney injury (AKI) is a frequent complication of sepsis, with a high mortality. Hallmarks of septic-AKI include inflammation, endothelial injury, and tissue hypoxia. Therefore, it would be of interest to develop therapeutic approaches for improving the microvascular damage in septic-AKI. Erythropoietin (EPO) is a well- known cytoprotective multifunctional hormone. Thus, the aim of this study was to evaluate the protective effects of EPO on microvascular injury in a murine model of endotoxemic AKI. Male Balb/c mice were divided into four groups: control, LPS (8 mg/kg, ip.), EPO (3000 IU / kg, sc.) and LPS + EPO. A time course study (0–48 h) was designed. Experiments include, among others, im- munohistochemistry and Western blottings of hypoxia-inducible transcription factor (HIF-1α), erythropoietin receptor (EPO-R), vascular endothelial growth factor system (VEGF/VEGFR-2), platelet and endothelial adhesion molecule-1 (PeCAM-1), inducible nitric oxide synthase (iNOS) and phosphorylated nuclear factor kappa B p65 (NF-κB). Data showed that EPO attenuates renal microvascular damage during septic-AKI progression through a) the decrease of HIF-1 alpha, iNOS, and NF-κB and b) the enhancement of EPO-R, PeCAM-1, VEGF, and VEGFR-2 expression. In summary, EPO renoprotection involves the attenuation of septic-induced renal hypoxia and inflammation as well as ameliorates the endotoxemic microvascular injury. 2021-06-08T23:46:01Z 2021-06-08T23:46:01Z 2018-08-15 Artículo Stoyanoff, Tania Romina, et. al., 2018. Erythropoietin attenuates LPS-induced microvascular damage in a murine model of septic acute kidney injury. Biomedicine of Pharmacotherapy. París: France-editions Scientifiques Medicales Elsevier, vol. 107, p. 1046-1055. ISSN 0753-3322. 0753-3322 http://repositorio.unne.edu.ar/handle/123456789/28093 eng openAccess http://creativecommons.org/licenses/by-nc-nd/2.5/ar/ application/pdf application/pdf France-editions Scientifiques Medicales Elsevier Biomedicine of Pharmacotherapy, 2018, vol. 107, p. 1046-1055.
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 Septic AKI
Erythropoietin
Hypoxia
Microvascular injury
spellingShingle Septic AKI
Erythropoietin
Hypoxia
Microvascular injury
Stoyanoff, Tania Romina
Rodríguez, Juan Pablo
Todaro, Juan Santiago
Melana Colavita, Juan Pablo
Torres, Adriana Mónica
Aguirre, María Victoria
Erythropoietin attenuates LPS-induced microvascular damage in a murine model of septic acute kidney injury
topic_facet Septic AKI
Erythropoietin
Hypoxia
Microvascular injury
description Acute kidney injury (AKI) is a frequent complication of sepsis, with a high mortality. Hallmarks of septic-AKI include inflammation, endothelial injury, and tissue hypoxia. Therefore, it would be of interest to develop therapeutic approaches for improving the microvascular damage in septic-AKI. Erythropoietin (EPO) is a well- known cytoprotective multifunctional hormone. Thus, the aim of this study was to evaluate the protective effects of EPO on microvascular injury in a murine model of endotoxemic AKI. Male Balb/c mice were divided into four groups: control, LPS (8 mg/kg, ip.), EPO (3000 IU / kg, sc.) and LPS + EPO. A time course study (0–48 h) was designed. Experiments include, among others, im- munohistochemistry and Western blottings of hypoxia-inducible transcription factor (HIF-1α), erythropoietin receptor (EPO-R), vascular endothelial growth factor system (VEGF/VEGFR-2), platelet and endothelial adhesion molecule-1 (PeCAM-1), inducible nitric oxide synthase (iNOS) and phosphorylated nuclear factor kappa B p65 (NF-κB). Data showed that EPO attenuates renal microvascular damage during septic-AKI progression through a) the decrease of HIF-1 alpha, iNOS, and NF-κB and b) the enhancement of EPO-R, PeCAM-1, VEGF, and VEGFR-2 expression. In summary, EPO renoprotection involves the attenuation of septic-induced renal hypoxia and inflammation as well as ameliorates the endotoxemic microvascular injury.
format Artículo
author Stoyanoff, Tania Romina
Rodríguez, Juan Pablo
Todaro, Juan Santiago
Melana Colavita, Juan Pablo
Torres, Adriana Mónica
Aguirre, María Victoria
author_facet Stoyanoff, Tania Romina
Rodríguez, Juan Pablo
Todaro, Juan Santiago
Melana Colavita, Juan Pablo
Torres, Adriana Mónica
Aguirre, María Victoria
author_sort Stoyanoff, Tania Romina
title Erythropoietin attenuates LPS-induced microvascular damage in a murine model of septic acute kidney injury
title_short Erythropoietin attenuates LPS-induced microvascular damage in a murine model of septic acute kidney injury
title_full Erythropoietin attenuates LPS-induced microvascular damage in a murine model of septic acute kidney injury
title_fullStr Erythropoietin attenuates LPS-induced microvascular damage in a murine model of septic acute kidney injury
title_full_unstemmed Erythropoietin attenuates LPS-induced microvascular damage in a murine model of septic acute kidney injury
title_sort erythropoietin attenuates lps-induced microvascular damage in a murine model of septic acute kidney injury
publisher France-editions Scientifiques Medicales Elsevier
publishDate 2021
url http://repositorio.unne.edu.ar/handle/123456789/28093
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