English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/215096
Share/Impact:
Statistics
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE
Exportar a otros formatos:

Title

Nrf2 Plays a Protective Role Against Intravascular Hemolysis-Mediated Acute Kidney Injury

AuthorsRubio-Navarro, Alfonso; Vázquez-Carballo, Cristina; Guerrero-Hue, Melania; García-Caballero, Cristina; Herencia, Carmen; Gutiérrez, Eduardo; Yuste, Claudia; Sevillano, Ángel; Praga, Manuel; Egea, Javier; Cannata, Pablo; Cortegano, Isabel ; Andrés, Belén de; Gaspar, María Luisa; Cadenas, Susana; Michalska, Patrycja; León, Rafael; Ortiz, Alberto; Egido, Jesús; Moreno, Juan Antonio
KeywordsIntravascular hemolysis
Hemoglobin
Heme
Nrf2
Oxidative stress
Tubular injury
Sulforaphane
Issue Date3-Jul-2019
CitationFrontiers in Pharmacology 10 (2019)
AbstractMassive intravascular hemolysis is associated with acute kidney injury (AKI). Nuclear factor erythroid-2-related factor 2 (Nrf2) plays a central role in the defense against oxidative stress by activating the expression of antioxidant proteins. We investigated the role of Nrf2 in intravascular hemolysis and whether Nrf2 activation protected against hemoglobin (Hb)/heme-mediated renal damage in vivo and in vitro. We observed renal Nrf2 activation in human hemolysis and in an experimental model of intravascular hemolysis promoted by phenylhydrazine intraperitoneal injection. In wild-type mice, Hb/heme released from intravascular hemolysis promoted AKI, resulting in decreased renal function, enhanced expression of tubular injury markers (KIM-1 and NGAL), oxidative and endoplasmic reticulum stress (ER), and cell death. These features were more severe in Nrf2-deficient mice, which showed decreased expression of Nrf2-related antioxidant enzymes, including heme oxygenase 1 (HO-1) and ferritin. Nrf2 activation with sulforaphane protected against Hb toxicity in mice and cultured tubular epithelial cells, ameliorating renal function and kidney injury and reducing cell stress and death. Nrf2 genotype or sulforaphane treatment did not influence the severity of hemolysis. In conclusion, our study identifies Nrf2 as a key molecule involved in protection against renal damage associated with hemolysis and opens novel therapeutic approaches to prevent renal damage in patients with severe hemolytic crisis. These findings provide new insights into novel aspects of Hb-mediated renal toxicity and may have important therapeutic implications for intravascular hemolysis-related diseases
Publisher version (URL)http://dx.doi.org/10.3389/fphar.2019.00740
URIhttp://hdl.handle.net/10261/215096
DOIhttp://dx.doi.org/10.3389/fphar.2019.00740
Identifiersdoi: 10.3389/fphar.2019.00740
issn: 1663-9812
Appears in Collections:(CBM) Artículos
Files in This Item:
File Description SizeFormat 
CadenasS_Nrf2PlaysaProtective.pdf11,72 MBAdobe PDFThumbnail
View/Open
Show full item record
Review this work
 


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.