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The effect of halofuginone, an inhibitor of collagen type I synthesis, on urethral stricture formation: In vivo and in vitro study in a rat model
Year:
2000
Source of publication :
Journal of Urology
Authors :
Genina, Olga
;
.
Pines, Mark
;
.
Volume :
164
Co-Authors:

Nagler, A., Dept. of Bone Marrow Trans./Urology, Hadassah University Hospital, Institute of Animal Science, Bet Dagan, Israel,
Gofrit, O., Dept. of Bone Marrow Trans./Urology, Hadassah University Hospital, Institute of Animal Science, Bet Dagan, Israel,
Ohana, M., Dept. of Bone Marrow Trans./Urology, Hadassah University Hospital, Institute of Animal Science, Bet Dagan, Israel,
Pode, D., Dept. of Bone Marrow Trans./Urology, Hadassah University Hospital, Institute of Animal Science, Bet Dagan, Israel,
Genina, O., Institute of Animal Science, Agricultural Research Organization, The Volcani Center, Bet Dagan, Israel
Pines, M., Institute of Animal Science, Agricultural Research Organization, The Volcani Center, Bet Dagan, Israel

Facilitators :
From page:
1776
To page:
1780
(
Total pages:
5
)
Abstract:
Purpose: Urethral strictures are narrowing of the urethra caused by fibrosis due to excessive collagen production in response to an insult. We evaluated the effects of halofuginone, a potent inhibitor of collagen α1(I) gene expression, on experimentally induced urethral strictures in vivo and on rat urethral fibroblasts in vitro. Materials and Methods: Applying coagulation current to the male rat urethra produced urethral strictures. Halofuginone was given to the animals for 7 days, starting on the day of stricture formation, either orally at 1 and 5 ppm in the diet or by injection of 0.03% halofuginone solution into the urethra. All rats were sacrificed on day 21. Collagen α1(I) gene expression was evaluated by in situ hybridization, collagen content by sirius red staining and urethral morphology by urethrogram. Results: Coagulation current produced reproducible strictures with a typical urethrogram appearance, which were associated with increases in collagen α1(I) gene expression and collagen content at the stricture site. Halofuginone injected into the urethra or orally at 5 ppm normalized the urethrogram and prevented increases in collagen α1(I) gene expression and collagen content. Halofuginone at a concentration of 10-8 M. inhibited the collagen secreted by fibroblasts derived from the rat male urethra, which was due to inhibition of the collagen α1(I) gene expression. Conclusions: Halofuginone prevented stricture formation and may become an important mode of therapy in the prevention of restenosis during urethral stricture formation.
Note:
Related Files :
Animal
animal cell
animal experiment
animal model
drug effect
Fibrosis
gene expression
Male
restenosis
Show More
Related Content
More details
DOI :
Article number:
0
Affiliations:
Database:
Scopus
Publication Type:
article
;
.
Language:
English
Editors' remarks:
ID:
27416
Last updated date:
02/03/2022 17:27
Creation date:
17/04/2018 00:30
Scientific Publication
The effect of halofuginone, an inhibitor of collagen type I synthesis, on urethral stricture formation: In vivo and in vitro study in a rat model
164

Nagler, A., Dept. of Bone Marrow Trans./Urology, Hadassah University Hospital, Institute of Animal Science, Bet Dagan, Israel,
Gofrit, O., Dept. of Bone Marrow Trans./Urology, Hadassah University Hospital, Institute of Animal Science, Bet Dagan, Israel,
Ohana, M., Dept. of Bone Marrow Trans./Urology, Hadassah University Hospital, Institute of Animal Science, Bet Dagan, Israel,
Pode, D., Dept. of Bone Marrow Trans./Urology, Hadassah University Hospital, Institute of Animal Science, Bet Dagan, Israel,
Genina, O., Institute of Animal Science, Agricultural Research Organization, The Volcani Center, Bet Dagan, Israel
Pines, M., Institute of Animal Science, Agricultural Research Organization, The Volcani Center, Bet Dagan, Israel

The effect of halofuginone, an inhibitor of collagen type I synthesis, on urethral stricture formation: In vivo and in vitro study in a rat model
Purpose: Urethral strictures are narrowing of the urethra caused by fibrosis due to excessive collagen production in response to an insult. We evaluated the effects of halofuginone, a potent inhibitor of collagen α1(I) gene expression, on experimentally induced urethral strictures in vivo and on rat urethral fibroblasts in vitro. Materials and Methods: Applying coagulation current to the male rat urethra produced urethral strictures. Halofuginone was given to the animals for 7 days, starting on the day of stricture formation, either orally at 1 and 5 ppm in the diet or by injection of 0.03% halofuginone solution into the urethra. All rats were sacrificed on day 21. Collagen α1(I) gene expression was evaluated by in situ hybridization, collagen content by sirius red staining and urethral morphology by urethrogram. Results: Coagulation current produced reproducible strictures with a typical urethrogram appearance, which were associated with increases in collagen α1(I) gene expression and collagen content at the stricture site. Halofuginone injected into the urethra or orally at 5 ppm normalized the urethrogram and prevented increases in collagen α1(I) gene expression and collagen content. Halofuginone at a concentration of 10-8 M. inhibited the collagen secreted by fibroblasts derived from the rat male urethra, which was due to inhibition of the collagen α1(I) gene expression. Conclusions: Halofuginone prevented stricture formation and may become an important mode of therapy in the prevention of restenosis during urethral stricture formation.
Scientific Publication
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