Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\30057686
.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Oxid+Med+Cell+Longev
2018 ; 2018
(ä): 8017073
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Flutamide Induces Hepatic Cell Death and Mitochondrial Dysfunction via Inhibition
of Nrf2-Mediated Heme Oxygenase-1
#MMPMID30057686
Zhang L
; Guo J
; Zhang Q
; Zhou W
; Li J
; Yin J
; Cui L
; Zhang T
; Zhao J
; Carmichael PL
; Middleton A
; Peng S
Oxid Med Cell Longev
2018[]; 2018
(ä): 8017073
PMID30057686
show ga
Flutamide is a widely used nonsteroidal antiandrogen for prostate cancer therapy,
but its clinical application is restricted by the concurrent liver injury.
Increasing evidence suggests that flutamide-induced liver injury is associated
with oxidative stress, though the precise mechanism is poorly understood. Nuclear
factor erythroid 2-related factor 2 (Nrf2) is a master transcription factor
regulating endogenous antioxidants including heme oxygenase-1 (HO-1). This study
was designed to delineate the role of Nrf2/HO-1 in flutamide-induced hepatic cell
injury. Our results showed that flutamide concentration dependently induced
cytotoxicity, hydrogen peroxide accumulation, and mitochondrial dysfunction as
indicated by mitochondrial membrane potential loss and ATP depletion. The protein
expression of Nrf2 and HO-1 was induced by flutamide at 12.5 ?M but was
downregulated by higher concentrations of flutamide. Silencing either Nrf2 or
HO-1 was found to aggravate flutamide-induced hydrogen peroxide accumulation and
mitochondrial dysfunction as well as inhibition of the Nrf2 pathway. Moreover,
preinduction of HO-1 by Copp significantly attenuated flutamide-induced oxidative
stress and mitochondrial dysfunction, while inhibition of HO-1 by Snpp aggravated
these deleterious effects. These findings suggest that flutamide-induced hepatic
cell death and mitochondrial dysfunction is assoicated with inhibition of
Nrf2-mediated HO-1. Pharmacologic intervention of Nrf2/HO-1 may provide a
promising therapeutic approach in flutamide-induced liver injury.