Collagenase Clostridium histolyticum (Xiaflex) for the Treatment of Urethral Stricture Disease in a Rat Model of Urethral Fibrosis.

Abstract

OBJECTIVE:

To evaluate the treatment effect of collagenase Clostridium histolyticum (CCH) in a rat model of urethral fibrosis.

MATERIALS AND METHODS:

Thirty male Sprague-Dawley rats (300-350 g) were divided into 5 groups. The rat urethra was injected with normal saline in the sham group and, in the other 4 groups, the rat urethra was injected with 10 μg of transforming growth factor beta 1 to create fibrosis of the urethra. Two weeks following transforming growth factor beta 1 injection, the rats were injected with varying doses of CCH or vehicles, depending on their group. The rats were then euthanized at 4 weeks after CCH or vehicle injection. Urethral tissue was harvested for histologic and molecular analyses. Type I and III collagen levels were evaluated by Western blot analysis.

RESULTS:

There was urethral fibrosis and to significant increase in collagen type I and III expressions in the urethral fibrosis group compared with the sham group (P <.05). Urethral injection of CCH appeared to be safe and significantly reduce urethral fibrosis as well as collagen type I and III expressions in the high-dose CCH treatment groups when compared with the treatment control group (P <.01).

CONCLUSION:

This study demonstrated a beneficial effect of CCH injections in a rat model of urethral fibrosis. These findings suggest a potential role for CCH as a therapeutic option in urethral stricture patients and warrant further investigation.

• Authors: Premsant Sangkum, Faysal A Yafi, Hogyoung Kim, Mostafa Bouljihad, Manish Ranjan, Amrita Datta, Sree Harsha Mandava, Suresh C Sikka, Asim B Abdel-Mageed, Krishnarao Moparty, Wayne J G Hellstrom
• Journal: Urology (Urology) Vol. 86 Issue 3 Pg. 647.e1-6 (Sep 2015) ISSN: 1527-9995 [Electronic] United States
• PMID: 26126692 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Microbial Collagenase

Topics

• Animals
• Disease Models, Animal
• Fibrosis (diagnosis, drug therapy)
• Male
• Microbial Collagenase (therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Urethra (drug effects, pathology)
• Urethral Stricture (drug therapy)