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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Am+J+Transl+Res
2016 ; 8
(11
): 4574-4585
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gab.com Text
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English Wikipedia
T-type calcium channel blocker attenuates unilateral ureteral obstruction-induced
renal interstitial fibrosis by activating the Nrf2 antioxidant pathway
#MMPMID27904663
Chung S
; Kim S
; Kim M
; Koh ES
; Yoon HE
; Kim HS
; Park CW
; Chang YS
; Shin SJ
Am J Transl Res
2016[]; 8
(11
): 4574-4585
PMID27904663
show ga
Besides its effect on high blood pressure, T-type calcium channel blocker is
renoprotective in experimental models of renal fibrosis. However, the exact
mechanism of T-type calcium channel blocker on tubulointerstitial fibrosis is
unclear. We investigated whether the renoprotective effect of T-type calcium
channel blocker is associated with modulation of the signaling of oxidative
stress-induced renal fibrosis. Treatment with a non-hypotensive dose of
efonidipine, a T-type calcium channel blocker, or nifedipine, an L-type channel
blocker, was initiated one day before unilateral ureteral obstruction (UUO) in
C57BL6/J mice, and was continued until 3 and 7 days after UUO. In the obstructed
kidneys, treatment with efonidipine significantly attenuated interstitial
fibrosis, collagen deposition and inflammation increased by UUO creation compared
with treatment with nifedipine. Additionally, efonidipine significantly increased
the expression of the antioxidant enzymes heme oxygenase-1, NAD(P)H: quinone
oxidoreductase 1, catalase and superoxide dismutase 1. Increased apoptotic cell
death and decreased B-cell lymphoma 2 expression were also significantly
ameliorated by efonidipine. The expression of the histone acetyltransferase
p300/CBP-associated factor, a regulator of inflammatory molecules, was
significantly inhibited by efonidipine. These beneficial effects of efonipidine
were attributed to the increased nuclear expression of nuclear
factor-erythroid-2-related factor 2 (Nrf2) on UUO day 3 and the increased
expressions of both total and nuclear Nrf2 with elevated Kelch-like
ECH-associated protein 1 on UUO day 7. The data indicate that T-type calcium
channel blocker exerts beneficial effects in renal interstitial fibrosis by
activating Nrf2 and subsequent antioxidant enzymes.