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- W2011444708 abstract "<i>Background/Aims:</i> 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. <i>Methods:</i> We administered AKF-PD to diabetic <i>db/db </i>mice for 12 weeks. Moreover, we performed in vitro cultures using murine mesangial cells exposed to high ambient glucose concentrations. <i>Results:</i> AKF-PD reduced renal hypertrophy, mesangial matrix expansion and albuminuria in the <i>db/db</i> mice. The upregulated expression of α<sub>1</sub>(I)- and α<sub>1</sub>(IV)-collagen and fibronectin mRNAs, transforming growth factor-β1 (TGF-β<sub>1</sub>), 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 <i>db</i>/<i>db</i> mice. The maximal effective dose of AKF-PD was about 500 mg/kg body weight. AKF-PD inhibited the upregulated expression of α<sub>1</sub>(I)- and α<sub>1</sub>(IV)-collagens, TGF-β<sub>1</sub>, TIMP-1 and α-SMA induced by high glucose concentrations in cultured mesangial cells. <i>Conclusions:</i> 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 <i>db/db </i>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." @default.
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- W2011444708 date "2011-01-01" @default.
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- W2011444708 title "Fluorofenidone Attenuates Diabetic Nephropathy and Kidney Fibrosis in <i>db/db</i> Mice" @default.
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- W2011444708 doi "https://doi.org/10.1159/000329419" @default.
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