Fluorofenidone attenuates diabetic nephropathy and kidney fibrosis in db/db mice.

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.

Fluorofenidone inhibits Ang II-induced apoptosis of renal tubular cells through blockage of the Fas/FasL pathway.

Objectives: The present study was designed to investigate the inhibitory effects of fluorofenidone on Ang II-induced apoptosis in renal tubular cells and the related signaling pathway.

Methods: Rat proximal tubular epithelial cells (NRK-52E) were used to examine the anti-apoptosis effects of fluorofenidone. Cell proliferation was assessed by methyl thiazolyl tetrazolium assay.

Fluorofenidone inhibits TGF-beta1 induced CTGF via MAPK pathways in mouse mesangial cells.

Objectives: The development of novel antifibrotic agent candidates for the treatment of diabetic nephropathy. The present study was designed to investigate the potential mechanism of fluorofenidone involving the downregulation of CTGF expression induced by TGF-beta1 and the related signaling pathway in mouse mesangial cells (MMCs).

Methods: Mouse mesangial cells were applied to explore the involvement of MAPK in TGF-beta1 signal pathway to CTGF, and the regulation of fluorofenidone.

Fluorofenidone attenuates collagen I and transforming growth factor-beta1 expression through a nicotinamide adenine dinucleotide phosphate oxidase-dependent way in NRK-52E cells.

Aim: Fluorofenidone (1-(3-fluorophenyl)-5-methyl-2-(1H)-pyridone) is a novel pyridone agent. The aim of the present study is to investigate the effects of fluorofenidone on angiotensin (Ang)II-induced fibrosis and the involved molecular mechanism in rat proximal tubular epithelial cells.

Methods: NRK-52E cells, a rat proximal tubular epithelial cell line, were incubated with medium containing AngII, with or without nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor diphenylene iodonium (DPI), losartan, fluorofenidone (2, 4 and 8 mmol/L) and pirfenidone (8 mmol/L) for 24 h.

[Losartan inhibits high glucose-induced CTGF expression via ERK1/2 MAPK pathways in mouse mesangial cells].

Aim: To investigate the effects and mechanism of losartan on expression of CTGF induced by high glucose.

Methods: Mouse mesangial cells (MMCs) were cultured in vitro, initially, MMCs were stimulated by high glucose(25 mmol/L glucose) for 24 h, 48 h, 72 h, the phosphorylation of ERK1/2 was assessed by Western blot. Then MMCs were randomly divided into 5 groups: (1) Low glucose group (5.

[Effect of enalapil on renal interstitial fibrosis in rats with unilateral ureteral obstruction].

Objective: To investigate the effect of enalapril on renal interstitial fibrosis in rats with unilateral ureteral obstruction(UUO).

Methods: UUO model was induced by ligating the left ureter in rats. Male Sprague-Dawley(SD) rats were randomly divided into a sham-operated group(n=16), a UUO model group(n=24), and an enalapril treated group(n=24).

[The effect of losartan on glomerular sclerosis in rats with diabetic nephropathy].

Objective: To explore the degradation mechanism of losartan on extracellular matrix in rats with diabetic nephropathy.

Methods: The rat model of diabetic nephropathy was established by streptozotozin(STZ) injection, and the rats were randomly divided into 3 groups: (a normal group, a model group and a losartan group). For 16 weeks, the serum creatinine and urea nitrogen were measured, and glomerular sclerosis index(GSI) were caculated.

[Expression of p27 and TGF-beta in rat kidney with unilateral ureteral obstruction and the relationship between TGF-beta and p27].

Aim: To explore the expression of p27 and the changes of TGF-beta in the renal tubule on the process of renal interstitial fibrosis caused by unilateral ureteral obstruction (UUO) in rats and to investigate the relationship between TGF-beta and p27 in renal interstitial fibrosis rats.

Methods: Sixty rats were randomly divided into sham-operated group (SOR) and UUO group. Ten rats from each group were sacrificed on days 7, 14 and 21 after operation respectively.

[Effect of losartan on the expressions of TGF-beta1, p-Smad2/3, and Smad7 in the remnant renal tissues of 5/6 nephrectomized rats].

Objective: To investigate the mechanism of losartan treating glomerulosclerosis and to observe the effect of losartan on the expressions of TGF-beta1, p-Smad2/3, and Smad7 in the renal tissues of 5/6 nephrectomized rats.

Methods: Male Wistar rats were randomly divided into a sham-operated group, a 5/6 nephrectomized model group, and a losartan treated group. The rats in the model group and the losartan treated group were performed 5/6 nephrectomy by the method with 2 procedures.

[Expression of p27 in rat kidney with unilateral ureteral obstruction and the therapeutic effect of enalapril].

Objective: To explore the effect of p27 in the renal tubule on the process of renal interstitial fibrosis caused by unilateral ureteral obstruction (UUO) in rats, and to examine the expression changes of p27 after enalapril intervention and to interpret the anti-fibrotic mechanism.

Methods: Ninety rats were randomly divided into the sham-operated group (SOR), UUO group,and UUO+enalapril treatment group [enalapril: 10 mg/(kg.d)].

[P21 expression in renal interstitial fibrosis and regulative effect of enalapril].

Objective: To investigate the expression of P21 in renal interstitial fibrosis rats and the effect of enalapril on it.

Methods: Sprague Dawley rats were randomly divided into 3 groups: a sham operation group,a unilateral urethral obstruction group, and an enalapril treatment group. The expression of P21 in renal tubular epithelial cells on the process was detected by immunohistochemistry at different time spots (7, 14, 21 d after UUO, sham-surgery or enalapril treatment).