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

Ning, Wangbin; Hu, Gaoyun; Peng, Zhangzhe; Wang, Wei; Chen, Jiying; Zheng, Xuan; Li, Jing; Tao, Ling

doi:10.1016/j.intimp.2011.04.016

Cited by 21 publications

(23 citation statements)

References 38 publications

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“…Moreover, fluorine compounds also have a high hydrophobicity, which can promote their absorption and transmission speed in vivo. In previous studies, AKF-PD has been proven to be a broad-spectrum antifibrosis drug, which could be used against renal fibrosis (34,45,48), pulmonary fibrosis (29), and myocardial fibrosis (8). Intriguingly, it is our…”

Section: Discussionmentioning

confidence: 99%

“…Many studies have reported that pyridone agents, such as pirfenidone (PFD), can attenuate fibrosis in many organs including pulmonary (21), cardiac (44), renal (39), and hepatic (10,11,32). As a newly developed water-soluble pyridone agent with potential broadspectrum antifibrotic characteristics, fluorofenidone [1-(3-fluorophenyl)-5-methyl-2-(1H)-pyridone; AKF-PD] can attenuate renal and cardiac fibrosis (8,34,45,48). However, the therapeutic effects on hepatic fibrosis remain unclear.…”

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confidence: 99%

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Fluorofenidone attenuates hepatic fibrosis by suppressing the proliferation and activation of hepatic stellate cells

Yang

Wang

et al. 2014

American Journal of Physiology-Gastrointestinal and Liver Physi

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Fluorofenidone attenuates hepatic fibrosis by suppressing the proliferation and activation of hepatic stellate cells

Yang

Wang

et al. 2014

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Our previous experimental data demonstrated FD exerts its anti-oxidative [12], anti-inflammation [13,14], and anti-fibrotic [8,9,15] potency in vivo and in vitro. Multiple cell signaling pathways, including MAPK [16], TGF-b1/Smads [17], and NF-jB [13], are involved in FD therapeutic intervention process.…”

Section: Introductionmentioning

confidence: 97%

Fluorofenidone protects against renal fibrosis by inhibiting STAT3 tyrosine phosphorylation

Tang

Liu

et al. 2015

Mol Cell Biochem

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Signaling through the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway, especially JAK2/STAT3, is involved in renal fibrosis. Fluorofenidone (FD), a novel pyridone agent, exerts anti-fibrotic effects in vitro and in vivo. Herein, we sought to investigate whether FD demonstrates its inhibitory function through preventing JAK2/STAT3 pathway. In this study, we examined the effect of FD on activation of rat renal interstitial fibroblasts, glomerular mesangial cells (GMC), and expression of JAK2/STAT3. Moreover, we explored the histological protection effects of FD in UUO rats, db/db mice, and phosphorylation of JAK2/STAT3 cascade. Our studies found that pretreatment with FD resulted in blockade of activation of fibroblast and GMC manifested by fibronectin (FN) and α-smooth muscle actin (α-SMA) protein expression and decline of STAT3 tyrosine phosphorylation induced by IL-6 or high glucose. In unilateral ureteral obstruction rats and a murine model of spontaneous type 2 diabetes (db/db mice), treatment with FD blocked the expression of FN and α-SMA, prevented renal fibrosis progression, and attenuated STAT3 activation. However, FD administration did not interfere with JAK2 activation both in vivo and in vitro. In summary, the molecular mechanism by which FD exhibits renoprotective effects appears to involve the inhibition of STAT3 phosphorylation.

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“…14,15 Fluorofenidone (AKF; 5-methyl-1-[3-fluorophenyl]-2-[1H]-pyridone) which has been synthesized by the Department of Pharmacochemistry, School of Pharmaceutical Sciences, Central South University (Changsha, China), has a similar chemical structure to PD. 16,17 It can reduce fibroblast growth and collagen synthesis of different organs. [18][19][20][21] Furthermore, AKF is able to attenuate bleomycin-induced experimental IPF by reducing inflammation, accelerating the production of caveolin 1, inhibiting the phosphorylated MAPK-signaling pathway, and limiting the fibrosis cytokine TGF-β.…”

Section: Introductionmentioning

confidence: 99%

Spermidine-mediated poly(lactic-<em>co</em>-glycolic acid) nanoparticles containing fluorofenidone for the treatment of idiopathic pulmonary fibrosis

Tang¹,

Li²,

Guo³

et al. 2017

IJN

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Idiopathic pulmonary fibrosis is a progressive, fatal lung disease with poor survival. The advances made in deciphering this disease have led to the approval of different antifibrotic molecules, such as pirfenidone and nintedanib. An increasing number of studies with particles (liposomes, nanoparticles [NPs], microspheres, nanopolymersomes, and nanoliposomes) modified with different functional groups have demonstrated improvement in lung-targeted drug delivery. In the present study, we prepared, characterized, and evaluated spermidine (Spd)-modified poly(lactic- co -glycolic acid) (PLGA) NPs as carriers for fluorofenidone (AKF) to improve the antifibrotic efficacy of this drug in the lung. Spd-AKF-PLGA NPs were prepared and functionalized by modified solvent evaporation with Spd and polyethylene glycol (PEG)-PLGA groups. The size of Spd-AKF-PLGA NPs was 172.5±4.3 nm. AKF release from NPs was shown to fit the Higuchi model. A549 cellular uptake of an Spd–coumarin (Cou)-6-PLGA NP group was found to be almost twice as high as that of the Cou-6-PLGA NP group. Free Spd and difluoromethylornithine (DFMO) were preincubated in A549 cells to prove uptake of Spd-Cou-6-PLGA NPs via a polyamine-transport system. As a result, the uptake of Spd-Cou-6-PLGA NPs significantly decreased with increased Spd concentrations in incubation. At higher Spd concentrations of 50 and 500 µM, uptake of Spd-Cou-6-PLGA NPs reduced 0.34- and 0.49-fold from that without Spd pretreatment. After pretreatment with DFMO for 36 hours, cellular uptake of Spd-Cou-6-PLGA NPs reached 1.26-fold compared to the untreated DFMO group. In a biodistribution study, the drug-targeting index of Spd-AKF-PLGA NPs in the lung was 3.62- and 4.66-fold that of AKF-PLGA NPs and AKF solution, respectively. This suggested that Spd-AKF-PLGA NPs accumulated effectively in the lung. Lung-histopathology changes and collagen deposition were observed by H&E staining and Masson staining in an efficacy study. In the Spd-AKF-PLGA NP group, damage was further improved compared to the AKF-PLGA NP group and AKF-solution group. The results indicated that Spd-AKF-PLGA NPs are able to be effective nanocarriers for anti–pulmonary fibrosis therapy.

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

Cited by 21 publications

References 38 publications

Fluorofenidone attenuates hepatic fibrosis by suppressing the proliferation and activation of hepatic stellate cells

Fluorofenidone attenuates hepatic fibrosis by suppressing the proliferation and activation of hepatic stellate cells

Fluorofenidone protects against renal fibrosis by inhibiting STAT3 tyrosine phosphorylation

Spermidine-mediated poly(lactic-<em>co</em>-glycolic acid) nanoparticles containing fluorofenidone for the treatment of idiopathic pulmonary fibrosis

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

Cited by 21 publications

References 38 publications

Fluorofenidone attenuates hepatic fibrosis by suppressing the proliferation and activation of hepatic stellate cells

Fluorofenidone attenuates hepatic fibrosis by suppressing the proliferation and activation of hepatic stellate cells

Fluorofenidone protects against renal fibrosis by inhibiting STAT3 tyrosine phosphorylation

Spermidine-mediated poly(lactic-<em>co</em>-glycolic acid)&nbsp;nanoparticles containing fluorofenidone for the treatment of idiopathic pulmonary fibrosis

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Spermidine-mediated poly(lactic-<em>co</em>-glycolic acid) nanoparticles containing fluorofenidone for the treatment of idiopathic pulmonary fibrosis