Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=26640409
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 276.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 276.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 276.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 276.79999999999995 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\26640409
.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Int+J+Med+Sci
2015 ; 12
(11
): 891-904
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Fimasartan, a Novel Angiotensin-Receptor Blocker, Protects against Renal
Inflammation and Fibrosis in Mice with Unilateral Ureteral Obstruction: the
Possible Role of Nrf2
#MMPMID26640409
Kim S
; Kim SJ
; Yoon HE
; Chung S
; Choi BS
; Park CW
; Shin SJ
Int J Med Sci
2015[]; 12
(11
): 891-904
PMID26640409
show ga
OBJECTIVES: A newly developed angiotensin II receptor blocker, fimasartan, is
effective in lowering blood pressure through its action on the renin-angiotensin
system. Renal interstitial fibrosis, believed to be due to oxidative injury, is
an end-stage process in the progression of chronic kidney disease. Nuclear factor
erythroid 2-related factor 2 (Nrf2) is known to regulate cellular oxidative
stress and induce expression of antioxidant genes. In this study we investigated
the role of Nrf2 in fimasartan-mediated antioxidant effects in mice with renal
fibrosis induced by unilateral ureteral obstruction (UUO). MATERIALS AND METHODS:
UUO was induced surgically in mice, followed by either no treatment with
fimasartan or the intraperitoneal administration of fimasartan (3 mg/kg/day). On
day 7, we evaluated the changes in the renin-angiotensin system (RAS) and the
expression of Nrf2 and its downstream antioxidant genes, as well as renal
inflammation, apoptosis, and fibrosis in the obstructed kidneys. The effect of
fimasartan on the Nrf2 pathway was also investigated in HK-2 cells stimulated by
tumor necrosis factor-?. RESULTS: The mice with surgically induced UUO showed
increased renal inflammation and fibrosis as evidenced by histopathologic
findings and total collagen content in the kidney. These effects were attenuated
in the obstructed kidneys of the fimasartan-treated mice. Fimasartan treatment
inhibited RAS activation and the expression of Nox1, Nox2, and Nox4. In contrast,
fimasartan upregulated the renal expression of Nrf2 and its downstream signaling
molecules (such as NQO1; HO-1; GSTa2 and GSTm3). Furthermore, it increased the
expression of antioxidant enzymes, including CuSOD, MnSOD, and catalase. The
fimasartan-treated mice had significantly less apoptosis on TUNEL staining, with
decreased levels of pro-apoptotic protein and increased levels of anti-apoptotic
protein. In the HK-2 cells, fimasartan treatment inhibited RAS activation,
decreased expression of mitogen-activated protein kinases (MAPKs), and
upregulated the Nrf2 pathway. CONCLUSIONS: These results suggest that fimasartan
has beneficial effects in reducing renal oxidative stress, inflammation, and
fibrosis. Possible mechanisms to explain these effects are inhibition of RAS and
MAPKs and upregulation of Nrf2 signaling, with subsequent induction of
antioxidant pathways.
|Angiotensin Receptor Antagonists/*therapeutic use
[MESH]