| Autor: |
Wang, Ling Hao, Liu, Ji Shi, Ning, Wang Bin, Yuan, Qiong Jing, Zhang, Fang Fang, Peng, Zhang Zhe, Lu, Miao Miao, Luo, Ren Na, Fu, Xiao, Hu, Gao Yun, Wang, Zhao He, Tao, Li Jian |
| Předmět: |
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| Zdroj: |
Pharmacology; 2011, Vol. 88 Issue 1/2, p88-99, 12p, 1 Chart, 9 Graphs |
| Abstrakt: |
Background/Aims: Fluorofenidone [1-(3-fluorophenyl)-5-methyl-2-(1H)-pyridone, AKF-PD], a novel pyridone agent, showed potent antifibrotic properties. The aim of the present study was to investigate the effects of AKF-PD on diabetic nephropathy and kidney fibrosis, and to obtain an insight into its mechanisms of action. Methods: We administered AKF-PD to diabetic db/db mice for 12 weeks. Moreover, we performed in vitro cultures using murine mesangial cells exposed to high ambient glucose concentrations. Results: AKF-PD reduced renal hypertrophy, mesangial matrix expansion and albuminuria in the db/db mice. The upregulated expression of α1(I)- and α1(IV)-collagen and fibronectin mRNAs, transforming growth factor-β1 (TGF-β1), α-smooth muscle actin (α-SMA), and tissue inhibitors of metalloproteinase 1 (TIMP-1) mRNAs and proteins was inhibited by AKF-PD treatment in the renal cortex of db/db mice. The maximal effective dose of AKF-PD was about 500 mg/kg body weight. AKF-PD inhibited the upregulated expression of α1(I)- and α1(IV)-collagens, TGF-β1, TIMP-1 and α-SMA induced by high glucose concentrations in cultured mesangial cells. Conclusions: Our data indicate that AKF-PD diminishes the abnormal accumulation of mesangial matrix through the inhibition of upregulated expression of TGF-β target genes in kidneys of db/db mice, resulting in attenuation of renal fibrosis and amelioration of renal dysfunction despite persistent hyperglycemia. Therefore, AKF-PD, a potent antifibrotic agent, holds great promise in the treatment of diabetic nephropathy. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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