Fluorofenidone attenuates diabetic nephropathy and kidney fibrosis in db/db mice.
Pharmacology
; 88(1-2): 88-99, 2011.
Article
em En
| MEDLINE
| ID: mdl-21847000
ABSTRACT
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-ß1 (TGF-ß1), 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-ß1, 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-ß 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.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Piridonas
/
Nefropatias Diabéticas
/
Hipoglicemiantes
/
Rim
/
Nefropatias
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
China