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Mefunidone attenuates tubulointerstitial fibrosis in a rat model of unilateral ureteral obstruction.


ABSTRACT: BACKGROUND:Inflammation has a crucial role in renal interstitial fibrosis, which is the common pathway of chronic kidney diseases. Mefunidone (MFD) is a new compound which could effectively inhibit the proliferation of renal fibroblasts in vitro. However, the overall effect of Mefunidone in renal fibrosis remains unknown. METHODS:Sprague-Dawley rats were randomly divided intro 6 groups: sham operation, unilateral ureteral obstruction (UUO), UUO/Mefunidone (25, 50, 100mg/kg/day) and UUO/PFD (500mg/kg/day). The rats were sacrificed respectively on days 3, 7, and 14 after the operation. Tubulointerstitial injury index, interstitial collagen deposition, expression of fibronectin (FN), ?-smooth muscle actin (?-SMA), type I and III collagen and the number of CD3+ and CD68+ cells were determined. The expressions of proinflammatory cytokines, p-ERK, p-I?B, and p-STAT3 were measured in human renal proximal tubular epithelial cells of HK-2 or macrophages. RESULTS:Mefunidone treatment significantly attenuated tubulointerstitial injury, interstitial collagen deposition, expression of FN, ?-SMA, type I and III collagen in the obstructive kidneys, which correlated with significantly reduced the number of T cells and macrophages in the obstructive kidneys. Mechanistically, Mefunidone significantly inhibited tumor necrosis factor-? (TNF-?-) or lipopolysaccharide (LPS)-induced production of proinflammatory cytokines. This effect is possibly due to the inhibition of phosphorylation of ERK, I?B, and STAT3. CONCLUSION:Mefunidone treatment attenuated tubulointerstitial fibrosis in a rat model of UUO, at least in part, through inhibition of inflammation.

SUBMITTER: Liu C 

PROVIDER: S-EPMC4456380 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Mefunidone attenuates tubulointerstitial fibrosis in a rat model of unilateral ureteral obstruction.

Liu Chunyan C   Mei Wenjuan W   Tang Juan J   Yuan Qiongjing Q   Huang Ling L   Lu Miaomiao M   Wu Lin L   Peng Zhangzhe Z   Meng Jie J   Yang Huixiang H   Shen Hong H   Lv Ben B   Hu Gaoyun G   Tao Lijian L  

PloS one 20150604 6


<h4>Background</h4>Inflammation has a crucial role in renal interstitial fibrosis, which is the common pathway of chronic kidney diseases. Mefunidone (MFD) is a new compound which could effectively inhibit the proliferation of renal fibroblasts in vitro. However, the overall effect of Mefunidone in renal fibrosis remains unknown.<h4>Methods</h4>Sprague-Dawley rats were randomly divided intro 6 groups: sham operation, unilateral ureteral obstruction (UUO), UUO/Mefunidone (25, 50, 100mg/kg/day) an  ...[more]

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