title: N-acetylcysteine alleviates angiotensin II-mediated renal fibrosis in mouse obstructed kidneys.
abstract: OBJECTIVE
  To investigate the effects of ROS scavenger N-acetylcysteine (NAC) on angiotensin II (Ang II)-mediated renal fibrosis in vivo and in vitro.
  
  
  METHODS
  Mice were subjected to unilateral ureteral obstruction (UUO), and then treated with vehicle or NAC (250 mg/kg, ip) for 7 days. Histological changes of the obstructed kidneys were observed with Masson's trichrome staining. ROS levels were detected with DHE staining. The expression of relevant proteins in the obstructed kidneys was assessed using Western blotting assays. Cultured rat renal fibroblast NRK-49F cells were used for in vitro experiments.
  
  
  RESULTS
  In the obstructed kidneys, Ang II levels were significantly elevated, and collagen I was accumulated in the interstitial spaces. Furthermore, ROS production and the expression of p47 (a key subunit of NADPH oxidase complexes) were increased in a time-dependent manner; the expression of fibronectin, α-SMA and TGF-β were upregulated. Administration of NAC significantly alleviated the fibrotic responses in the obstructed kidneys. In cultured NRK-49F cells, treatment with Ang II (0.001-10 μmol/L) increased the expression of fibronectin, collagen I, α-SMA and TGF-β in dose-dependent and time-dependent manners. Ang II also increased ROS production and the phosphorylation of Smad3. Pretreatment with NAC (5 μmol/L) blocked Ang II-induced oxidative stress and ECM production in the cells.
  
  
  CONCLUSIONS
  In mouse obstructed kidneys, the fibrotic responses result from Ang II upregulation can be alleviated by the ROS scavenger N-acetylcysteine.
authors.affiliation: Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Nai-Jun
authors.initials: NJ
authors.lastname: Miao
authors.affiliation: Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Jin-Lan
authors.initials: JL
authors.lastname: Xu
authors.affiliation: Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Xin-Xin
authors.initials: XX
authors.lastname: Gan
authors.affiliation: Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Xu
authors.affiliation: Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Xue
authors.affiliation: Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Li-Min
authors.initials: LM
authors.lastname: Lu
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology / Q000627:therapeutic use*; D000804:Angiotensin II / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D002460:Cell Line; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology; D005355:Fibrosis / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007674:Kidney Diseases / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects; D014517:Ureteral Obstruction / Q000150:complications / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D000804:Angiotensin II; D000111:Acetylcysteine