Curcumin Attenuates Gentamicin-Induced Kidney Mitochondrial Alterations: Possible Role of a Mitochondrial Biogenesis Mechanism.
It has been shown that curcumin (CUR), a polyphenol derived from Curcuma longa, exerts a protective effect against gentamicin- (GM-) induced nephrotoxicity in rats, associated with a preservation of the antioxidant status. Although mitochondrial dysfunction is a hallmark in the GM-induced renal injury, the role of CUR in mitochondrial protection has not been studied. In this work, LLC-PK1 cells were preincubated 24 h with CUR and then coincubated 48 h with CUR and 8 mM GM. Treatment with CUR attenuated GM-induced drop in cell viability and led to an increase in nuclear factor (erythroid-2)-related factor 2 (Nrf2) nuclear accumulation and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) cell expression attenuating GM-induced losses in these proteins. In vivo, Wistar rats were injected subcutaneously with GM (75 mg/Kg/12 h) during 7 days to develop kidney mitochondrial alterations. CUR (400 mg/Kg/day) was administered orally 5 days before and during the GM exposure. The GM-induced mitochondrial alterations in ultrastructure and bioenergetics as well as decrease in activities of respiratory complexes I and IV and induction of calcium-dependent permeability transition were mostly attenuated by CUR. Protection of CUR against GM-induced nephrotoxicity could be in part mediated by maintenance of mitochondrial functions and biogenesis with some participation of the nuclear factor Nrf2.
Departamento de Biología, Facultad de Química, UNAM, 04510 Ciudad de México, DF, Mexico.
Mario
M
Negrette-Guzmán
Departamento de Biomedicina Cardiovascular, Instituto Nacional de Cardiología "Ignacio Chávez", 14080 Ciudad de México, DF, Mexico.
Wylly Ramsés
WR
García-Niño
Laboratorio de Fisiopatología Renal, Instituto Nacional de Cardiología "Ignacio Chávez", 14080 Ciudad de México, DF, Mexico.
Edilia
E
Tapia
Departamento de Biomedicina Cardiovascular, Instituto Nacional de Cardiología "Ignacio Chávez", 14080 Ciudad de México, DF, Mexico.
Cecilia
C
Zazueta
Unidad de Investigación en Enfermedades Oncológicas, Hospital Infantil de México "Federico Gómez", 06720 Ciudad de México, DF, Mexico.
Sara
S
Huerta-Yepez
Departamento de Patología, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", 14000 Ciudad de México, DF, Mexico.
Juan Carlos
JC
León-Contreras
Departamento de Patología, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", 14000 Ciudad de México, DF, Mexico.
Rogelio
R
Hernández-Pando
Departamento de Biología, Facultad de Química, UNAM, 04510 Ciudad de México, DF, Mexico.
Omar Emiliano
OE
Aparicio-Trejo
Departamento de Nefrología, Instituto Nacional de Cardiología "Ignacio Chávez", 14080 Ciudad de México, DF, Mexico.
Magdalena
M
Madero
Departamento de Biología, Facultad de Química, UNAM, 04510 Ciudad de México, DF, Mexico.
José
J
Pedraza-Chaverri