title: Rutin ameliorates renal fibrosis and proteinuria in 5/6-nephrectomized rats by anti-oxidation and inhibiting activation of TGFβ1-smad signaling.
abstract: OBJECTIVE
  Rutin, a polyphenolic flavonoid, was reported to have beneficial effect on drug induced nephropathy. The present study aimed to introduce 5/6 nephrectomized rat model to further evaluate its renal protective effect.
  
  
  METHODS
  Adult Wistar rats were induced to develop chronic renal failure through 5/6 nephrectomy (5/6 Nx). After that, animals were treated orally with saline, rutin at 15 and 45 mg/kg, and losartan (10 mg/kg) daily for 20 weeks; sham-operated animals were also involved as control. After treatment for 8 and 20 weeks, blood and urine samples were collected for biochemical examination; all the kidney remnants were collected for histological examination. The protein levels of TGF-β1, smad2 and phosphorylated-smad2 (p-smad2) in kidney were measured. Immunohistochemistry was used to analyze the expression of TGF-β1, fibronectin and collagen IV in kidney tissues.
  
  
  RESULTS
  Results suggested that rutin could reduce the proteinurea, blood urine nitrogen and blood creatinine in 5/6 Nx animals significantly, as well as oxidation stress in the kidney. By histological examination, rutin administration alleviated glomerular sclerosis scores and tubulointerstitial injuries in a dose-dependent manner (P<0.01). Immunohistochemistry also suggested rutin could reduce the expression of TGF-β1, fibronectin and collagen IV in kidney tissues. By western blot, we found the rutin could reduce the TGF-β1, p-smad2 expression in the kidney tissues of rats.
  
  
  CONCLUSIONS
  This study suggests that the rutin can improve renal function in 5/6 Nx rats effectively. Its effect may be due to its anti-oxidation and inhibiting TGFβ1-Smad signaling.
authors.affiliation: Department of Urology Surgery, Chinese PLA General Hospital Beijing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Urology Surgery, Chinese PLA General Hospital Beijing, China.
authors.forename: Jin-Shan
authors.initials: JS
authors.lastname: Lu
authors.affiliation: Department of Urology Surgery, Chinese PLA General Hospital Beijing, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Urology Surgery, Chinese PLA General Hospital Beijing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Urology Surgery, Chinese PLA General Hospital Beijing, China.
authors.forename: Bao-Fa
authors.initials: BF
authors.lastname: Hong
mesh_terms: D000818:Animals; D005355:Fibrosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009392:Nephrectomy; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D011507:Proteinuria / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012431:Rutin / Q000494:pharmacology / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects*; D051785:Smad Proteins / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D051785:Smad Proteins; D053773:Transforming Growth Factor beta1; D012431:Rutin
keywords: 5/6 nephrectomy; Rutin; TGF-β1; chronic renal failure