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

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.