Halofuginone reduces the occurrence of renal fibrosis in 5/6 nephrectomized rats.
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.
Benchetrit
Sydney
S
Department of Nephrology and Hypertension, Sapir Medical Center, Kfar Saba, Israel.
Yarkoni
Shy
S
Rathaus
Mauro
M
Pines
Marc
M
Rashid
Gloria
G
Bernheim
Joelle
J
Bernheim
Jacques
J
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
D010880:Piperidines; D011500:Protein Synthesis Inhibitors; D052999:Quinazolinones; C010176:halofuginone