title: Fluorofenidone attenuates oxidative stress and renal fibrosis in obstructive nephropathy via blocking NOX2 (gp91phox) expression and inhibiting ERK/MAPK signaling pathway.
abstract: OBJECTIVE
  We evaluated the therapeutic effects of fluorofenidone (AKF-PD), a novel pyridone agent, targeting oxidative stress and fibrosis in obstructive nephropathy.
  
  
  METHODS
  AKF-PD was used to treat renal interstitial fibrosis in unilateral ureteral obstruction (UUO) obstructive nephropathy in rats. The expression of NOX2 (gp91phox), fibronectin and extracellular signal regulated kinase (ERK) were detected by western blot. A level of Malondialdehyde (MDA), an oxidative stress marker, was measured by ELISA. In addition, ROS and the expressions of NOX2, collagen I (a1), fibronectin and p-ERK were measured in angiotensin (Ang) II-stimulated rat proximal tubular epithelial cells (NRK-52E) in culture.
  
  
  RESULTS
  In NRK-52E cells, AKF-PD reduced AngII induced expressions of ROS, NOX2, fibronectin, collagen I (a1) and p-ERK. In UUO kidney cortex, AKF-PD attenuated the degree of renal interstitial fibrosis, which was associated with reduced the expressions of collagen I (a1) and fibronectin. Furthermore, AKF-PD downregulated the expressions of NOX2, MDA and p-ERK.
  
  
  CONCLUSIONS
  AKF-PD treatment inhibits the progression of renal interstitial fibrosis by suppressing oxidative stress and ERK/MAPK signaling pathway.
authors.forename: Jiao
authors.initials: J
authors.lastname: Qin
authors.forename: Wen-Juan
authors.initials: WJ
authors.lastname: Mei
authors.forename: Yan-Yun
authors.initials: YY
authors.lastname: Xie
authors.forename: Ling
authors.initials: L
authors.lastname: Huang
authors.forename: Qiong-Jing
authors.initials: QJ
authors.lastname: Yuan
authors.forename: Gao-Yun
authors.initials: GY
authors.lastname: Hu
authors.forename: Li-Jian
authors.initials: LJ
authors.lastname: Tao
authors.forename: Zhang-Zhe
authors.initials: ZZ
authors.lastname: Peng
mesh_terms: D000818:Animals; D005355:Fibrosis; D015971:Gene Expression Regulation, Enzymologic; D007674:Kidney Diseases / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D011728:Pyridones / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C511655:5-methyl-1-(3-fluorophenyl)-2-(1H)-pyridone; D008562:Membrane Glycoproteins; D011728:Pyridones; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases