Korean J Urol.  2009 Aug;50(8):805-811. 10.4111/kju.2009.50.8.805.

Effect of Mitomycin-C on Experimentally Induced Urethral Stricture in Rats

• Shin DE
• Kim CS
• Rho J
• Moon HY

• KMID: 1780486
• DOI: http://doi.org/10.4111/kju.2009.50.8.805

Abstract

PURPOSE
Urethral stricture is a fibrotic process and, although it is one of the oldest known urologic diseases, it remains a common problem with a high recurrence rate. Mitomycin-C has been reported to have anti-replication properties in animal and clinical studies. The aim of this study was to observe the intraurethral impact of the use of mitomycin-C on scar formation and fibrosis in an experimental rat model of urethral stricture. MATERIALS AND METHODS: Twelve male Sprague-Dawley rats were used. With the animals under deep anesthesia, an internal urethrotomy was made with a cold knife. After the urethral injury, the rats were grouped randomly as follows: group 1 (control, n=4), group 2 (3 mg/l of mitomycin-C, n=4), and group 3 (5 mg/l of mitomycin-C, n=4). The rats were sacrificed 14 days later to evaluate epithelial proliferation and fibrosis. The penile urethra was removed and histopathologically examined by H&E staining, Masson trichrome staining, and immunohistochemistry with anti-collagen type I antibody. RESULTS: The stained specimens were examined under a light microscope. The extent of fibrosis and re-epithelization after urethral injury was greater in the areas with trauma than in those without. These findings were significantly reduced in the groups treated with mitomycin-C as compared with group 1, but there was no statistical difference between group 2 and group 3. Mitomycin-C treatment also prevented increases in collagen type I, whereas group 1 showed increases in collagen type I and collagen contents at the stricture site. CONCLUSIONS: These results suggest that mitomycin-C might inhibit the renewal of the epithelium and the synthesis of collagen secreted by fibroblasts in the affected urethra and then prevent scar formation. This raises the possibility of the use of mitomycin-C to prevent urethral stricture caused by trauma.

Keyword

Fibrosis; Mitomycin; Urethral stricture

MeSH Terms

Anesthesia
Animals
Cicatrix
Cold Temperature
Collagen
Collagen Type I
Constriction, Pathologic
Epithelium
Fibroblasts
Fibrosis
Humans
Immunohistochemistry
Light
Male
Mitomycin
Rats
Rats, Sprague-Dawley
Recurrence
Urethra
Urethral Stricture
Urologic Diseases
Collagen
Collagen Type I
Mitomycin

Figure

• 

  Fig. 1 Urethral injury, which was induced by a cold knife, was confirmed by severe bleeding at the sites of urethrotomy (arrows in A) on postoperative day (POD) 7 in the preliminary study. After the urethral injury, the rats were grouped into untreated (B) and mitomycin-C (MMC, 3 mg) treated (C) groups until POD 14. The extent of fibrosis (black arrow) and re-epithelization (white arrow) was measured at the sites of urethrotomy (D and E). Less fibrosis and re-epithelization was observed in MMC-treated groups than in the untreated group, whereas there were no dose-dependent changes in the MMC-treated groups (figures not shown for MMC 5 mg group). Scale bar (in A)=200 µm in (A), (B), and (C) and 50 µm in (D) and (E).

• 

  Fig. 2 Fibrosis was analyzed by Masson trichrome staining and immunohistochemistry. Collagen appeared blue by Masson trichrome stain (A, D, and G) and a greater intensity of increased deposition was seen in the untreated group 1 compared with the mitomycin-C (MMC)-treated groups. Immunohistochemistry with anti-collagen type I antibody also showed an increase in the untreated group (E and F, arrows), whereas there was less collagen type I at the time of urethral injury (B and C) and in the MMC-treated groups (H and I, arrows). Arrows in (A) indicate the sites of urethrotomy. Scale bar (in I)=200 µm in (A), (B), (D), (E), (G), and (H) and 50 µm in (C), (F), and (I).

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