Effect of Nintedanib on healing and fibrosis in rats with experimentally induced urethral injury.

ABSTRACT

AIM: We aimed to determine the effectiveness of Nintedanib treatment, which has known antifibrotic effect, in preventing fibrosis after urethral trauma. MATERIAL AND METHODS: Twenty-three adult Sprague-Dawley rats were divided randomly into 3 different groups Sham, Urethral injury group (UI) and Urethral injury+ Nintedanib (UI+N). The urethral injury model was made with a pediatric urethrotome knife. Nintedanib was administered at a dose of 50mg/kg by oral gavage for 14 days at the same time every day. After 14 days of treatment, all rats were performed penectomy under general anesthesia. Urethral tissue was evaluated histopathologically (congestion, inflammatory cell infiltration and spongiofibrosis) and immunohistochemically (transforming growth factor (TBF) Beta-1 and vascular endothelial growth factor receptor 2 (VEBFR2)). RESULTS: Histopathological findings: Group UI had higher scores in all categories (congestion, inflammatory cell infiltration, and spongiofibrosis), followed by Group UI+N and Group Sham, respectively. A statistically significant difference was found between Group UI and Group UI+N in terms of the scores of histopathological parameters (p<0.05). Immunohistochemical findings: Group UI had higher scores in both categories, followed by Group UI+N and Group Sham, respectively. A statistically significant difference was found between Group UI and Group UI+N in TGF Beta-1 and VEGF scores (p<0.05). CONCLUSION: We found that Nintedanib administration after urethral trauma reduced inflammation and fibrosis histologically and immunohistochemically. The positive effect of Nintedanib on inflammation and fibrosis after urethral trauma reported in this animal study is encouraging for a potential clinical human application.