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Morphological effects of mitomycin C on urothelial responses to experimentally-induced urethral stricture in rats
In Youb Chang1, Jin Nam Kim2, Sun-Ouck Kim3
1Department of Anatomy, College of Medicine, Chosun University.
Objectives:
To analyze the urothelial responses to mitomycin C treatment after urethral injury in rats, as the urothelium might play a role in the pathogenesis of urethral stricture.
Methods:
Male Sprague-Dawley rats were divided into four groups (n = 5/group): negative control, positive control without further treatment, experimental control treated with sodium hyaluronate and sodium carboxymethylcellulose, and experimental treated with mitomycin C after internal urethrotomy.
Results:
Compared with negative controls, positive controls showed a significant increase in cell proliferation and DNA damage accompanied by a considerable decrease in DNA repair in the urothelium, which resulted in urethral stricture. Experimental controls showed a significant increase in cell proliferation, DNA damage and DNA repair compared with negative controls. The mitomycin C-treated group showed a significant decrease in cell proliferation and DNA damage, but a considerable increase in DNA repair compared with the positive and experimental control groups. DNA damage was immediately increased after urethral injury, but DNA repair and cell proliferation showed belated and upregulated expression after mitomycin C treatment.
Conclusions:
Mitomycin C could induce healthy re-epithelialization without severe damage in the urothelium. This finding might support the possibility of using mitomycin C as an adjuvant therapy for urethral strictures, and it might also suggest a urothelial role in the process of urethral stricture after urethral injury.
Insights
Mitomycin-C treatment after urethral injury in rats promoted urothelial healing by reducing DNA damage and increasing DNA repair, suggesting its potential for treating urethral strictures.
Area of Science:
- Urology
- Regenerative Medicine
- Wound Healing
Background:
- Urethral stricture pathogenesis involves urothelial responses to injury.
- The urothelium's role in urethral stricture formation requires further investigation.
Purpose of the Study:
- To analyze urothelial responses to mitomycin-C treatment following urethral injury in a rat model.
- To evaluate the potential of mitomycin-C as an adjuvant therapy for urethral strictures.
Main Methods:
- Male Sprague-Dawley rats underwent internal urethrotomy and were divided into four groups: negative control, positive control, experimental control (sodium hyaluronate/carboxymethylcellulose), and mitomycin-C treated.
- Urothelial cell proliferation, DNA damage, and DNA repair were assessed.
Main Results:
- Urethral injury increased urothelial cell proliferation and DNA damage while decreasing DNA repair, leading to stricture.
- Mitomycin-C treatment significantly decreased cell proliferation and DNA damage but increased DNA repair compared to control groups.
- Mitomycin-C induced belated but upregulated urothelial cell proliferation and DNA repair post-injury.
Conclusions:
- Mitomycin-C facilitates healthy urothelial re-epithelialization with minimal damage after urethral injury.
- Mitomycin-C shows promise as an adjuvant therapy for urethral strictures.
- These findings highlight a potential urothelial role in urethral stricture development.
