title: Halofuginone reduces the occurrence of renal fibrosis in 5/6 nephrectomized rats.
abstract: BACKGROUND
  Halofuginone is a novel antifibrotic agent that can reverse the fibrotic process by specific inhibition of collagen type I synthesis.
  
  
  OBJECTIVE
  To evaluate the effect of Halo on the development of glomerulosclerosis and interstitial fibrosis in the 5/6 nephrectomy rat model
  
  
  METHODS
  Male Wistar rats were assigned to undergo 5/6 NX or sham operation, and then divided into three groups: 5/6 NX rats (NX-Halo and NX-Control) and sham. Systolic blood pressure, proteinuria and body weight were determined every 2 weeks. At sacrifice (10 weeks) creatinine clearance was evaluated and remnant kidneys removed for histologic examination, sirius red staining and in situ hybridization
  
  
  RESULTS
  Systolic blood pressure increased progressively in both 5/6 NX groups. Halo slowed the increase in proteinuria in 5/6 NX rats. As expected, creatinine clearance was lower in 5/6 NX groups when compared to sham rats. Creatinine clearance was significantly higher in the NX-Halo group at the end of the study period. Histologic examination by light microscopy showed significantly less severe interstitial fibrosis and glomerulosclerosis in Halo-treated rats. The increase in collagen alpha1 (I) gene expression and collagen staining after nephrectomy was almost completely abolished by Halo.
  
  
  CONCLUSIONS
  Halofuginone reduced proteinuria as well as the severity of interstitial fibrosis and glomerulosclerosis in 5/6 NX rats. The renal beneficial effect of Halo was also demonstrated by the blunted decrease in creatinine clearance observed in the treated animals.
authors.affiliation: Department of Nephrology and Hypertension, Sapir Medical Center, Kfar Saba, Israel.
authors.forename: Sydney
authors.initials: S
authors.lastname: Benchetrit
authors.forename: Shy
authors.initials: S
authors.lastname: Yarkoni
authors.forename: Mauro
authors.initials: M
authors.lastname: Rathaus
authors.forename: Marc
authors.initials: M
authors.lastname: Pines
authors.forename: Gloria
authors.initials: G
authors.lastname: Rashid
authors.forename: Joelle
authors.initials: J
authors.lastname: Bernheim
authors.forename: Jacques
authors.initials: J
authors.lastname: Bernheim
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D016022:Case-Control Studies; D004195:Disease Models, Animal; D005355:Fibrosis; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009392:Nephrectomy; D010880:Piperidines / Q000494:pharmacology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D011507:Proteinuria / Q000188:drug therapy; D052999:Quinazolinones / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D010880:Piperidines; D011500:Protein Synthesis Inhibitors; D052999:Quinazolinones; C010176:halofuginone