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עמוד בית
Thu, 10.10.24

Original Articles

IMAJ | volume 9

Journal 1, January 2007
pages: 30-34

Halofuginone Reduces the Occurrence of Renal Fibrosis in 5/6 Nephrectomized Rats

    Summary

    Background: Halofuginone is a novel antifibrotic agent that can reserve the fibrotic process by specific inhibition of collagen type I synthesis.

    Objectives: 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 α1 (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.  

     

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