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
Aporte de:
RIUNNE - Repositorio Institucional de la Universidad Nacional del Nordeste (UNNE) de Universidad Nacional del Nordeste
Descripción
Sumario: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.

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