Morphological effects of mitomycin C on urothelial responses to experimentally‐induced urethral stricture in rats

Abstract

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.

Prevention of urethral fibrosis induced by transforming growth factor beta 1 using selective Wnt/β‐catenin signaling inhibitors in a rat model

“…21,22 Various anti-fibrotic agents have been used to treat urethral strictures in previous studies, including collagenase, mitomycin C, and rapamycin. [23][24][25] Unfortunately, none of these drugs have been sufficiently proven to be effective at inhibiting urethral strictures. 26 Considering the mechanisms of fibrosis, there is a need to identify therapeutic agents against the more fundamental fibrosis process.…”

“…Various anti‐fibrotic agents have been used to treat urethral strictures in previous studies, including collagenase, mitomycin C, and rapamycin 23–25 . Unfortunately, none of these drugs have been sufficiently proven to be effective at inhibiting urethral strictures 26 .…”

Fabrication of Tissue-Engineered Bionic Urethra Using Cell Sheet Technology and Labeling By Ultrasmall Superparamagnetic Iron Oxide for Full-Thickness Urethral Reconstruction

“…Furthermore, some chemicals have been reported to have the ability to induce urethral fibrosis in animal models, such as transforming growth factor-beta 1 52 and mitomycin C 53. However, such urethral injuries may be superficial and offer a relatively good prognosis, but clinical instances of urethral stricture are generally associated with full-thickness urethra defects and are hard to repair.…”

Editorial Comment to Morphological effects of mitomycin C on urothelial responses to experimentally‐induced urethral stricture in rats

“…Chang et al . should be commended for providing further evidence that MMC not only inhibits cellular damage and fibroblast proliferation, but also upregulates urothelial cell DNA repair and induction of re‐epithelialization . Although the mechanism by which MMC creates this effect is unclear, this study suggests mitomycin C could have other potential applications where urinary tract damage requires urothelial regeneration.…”