RT Journal Article
T1 Nrf2 Plays a Protective Role Against Intravascular Hemolysis-Mediated Acute Kidney Injury.
A1 Rubio-Navarro, Alfonso
A1 Vazquez-Carballo, Cristina
A1 Guerrero-Hue, Melania
A1 Garcia-Caballero, Cristina
A1 Herencia, Carmen
A1 Gutierrez, Eduardo
A1 Yuste, Claudia
A1 Sevillano, Angel
A1 Praga, Manuel
A1 Egea, Javier
A1 Cannata, Pablo
A1 Cortegano, Isabel
A1 de Andres, Belen
A1 Gaspar, Maria Luisa
A1 Cadenas, Susana
A1 Michalska, Patrycja
A1 Leon, Rafael
A1 Ortiz, Alberto
A1 Egido, Jesus
A1 Moreno, Juan Antonio
K1 Nrf2
K1 Heme
K1 Hemoglobin
K1 Intravascular hemolysis
K1 Oxidative stress
K1 Sulforaphane
K1 Tubular injury
AB Massive 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.
SN 1663-9812
YR 2019
FD 2019-06-07
LK http://hdl.handle.net/10668/14287
UL http://hdl.handle.net/10668/14287
LA en
NO Rubio-Navarro A, Vázquez-Carballo C, Guerrero-Hue M, García-Caballero C, Herencia C, Gutiérrez E, et al. Nrf2 Plays a Protective Role Against Intravascular Hemolysis-Mediated Acute Kidney Injury. Front Pharmacol. 2019 Jul 3;10:740
DS RISalud
RD Mar 14, 2025