World journal of urology · 2025
Effects of antifibrotic agent Nintedanib on experimentally generated priapism model in rats.
СтатьяНазвание и аннотация: Перевод в очереди
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Çeker Gökhan, Girgin Reha, Cinar Onder, Kaymaz Esin, Erdem Salih, Turan Inci
Аннотация
PURPOSE: This study investigated the effects of Nintedanib, a triple tyrosine kinase inhibitor, on cavernosal tissues in a rat model of ischemic priapism (IP), focusing on fibrosis and erectile function.
METHODS: Sixty male Wistar Albino rats were divided into five groups (n = 12): Group 1 (control), Group 2 (1-hour IP + penectomy), Group 3 (1-hour IP + 6-week follow-up), Group 4 (1-hour IP + Nintedanib treatment for 6 weeks), and Group 5 (Nintedanib only). Erectile function was evaluated via intracavernosal pressure (ICP) during nerve stimulation. Fibrosis was assessed using Masson's trichrome staining and immunohistochemistry for VEGFR-2, PDGFR-β, and FGF-1. Oxidative stress markers (MDA, GSH, SOD) and growth factors were analyzed via ELISA and spectrophotometry. Statistical analysis used Kruskal-Wallis and Mann-Whitney U tests (p < 0.05).
RESULTS: Group 4 had significantly lower mean intracavernosal pressure (MeICP) values (median 26.5 mmHg) than Group 3 (49 mmHg) (p < 0.001). Masson's trichrome showed highest fibrosis in Group 4 (score 3 [2-4]) compared to Group 3 (score 3 [1-4]) (p < 0.001). VEGFR-2 ELISA levels dropped in Group 4 (6.55 ng/mL [5.5-7.1]) vs. Group 3 (7.75 ng/mL [7-7.9]) (p < 0.001). MDA levels peaked in Group 4 (33.66 nmol/g [24.39-45.39]), while GSH values remained comparable between Groups 3 and 4. SOD increased significantly in Groups 2-4 (Group 4: 6.25 ng/mL [5.2-7.0]) compared to Group 1 (4.95 ng/mL [3.9-5.6]) (p < 0.001).
CONCLUSION: Although Nintedanib is antifibrotic in pulmonary contexts, it appears to promote penile fibrosis post-IP, likely via excessive VEGFR-2 inhibition, impairing vascular recovery and erectile function. Further studies are needed.
METHODS: Sixty male Wistar Albino rats were divided into five groups (n = 12): Group 1 (control), Group 2 (1-hour IP + penectomy), Group 3 (1-hour IP + 6-week follow-up), Group 4 (1-hour IP + Nintedanib treatment for 6 weeks), and Group 5 (Nintedanib only). Erectile function was evaluated via intracavernosal pressure (ICP) during nerve stimulation. Fibrosis was assessed using Masson's trichrome staining and immunohistochemistry for VEGFR-2, PDGFR-β, and FGF-1. Oxidative stress markers (MDA, GSH, SOD) and growth factors were analyzed via ELISA and spectrophotometry. Statistical analysis used Kruskal-Wallis and Mann-Whitney U tests (p < 0.05).
RESULTS: Group 4 had significantly lower mean intracavernosal pressure (MeICP) values (median 26.5 mmHg) than Group 3 (49 mmHg) (p < 0.001). Masson's trichrome showed highest fibrosis in Group 4 (score 3 [2-4]) compared to Group 3 (score 3 [1-4]) (p < 0.001). VEGFR-2 ELISA levels dropped in Group 4 (6.55 ng/mL [5.5-7.1]) vs. Group 3 (7.75 ng/mL [7-7.9]) (p < 0.001). MDA levels peaked in Group 4 (33.66 nmol/g [24.39-45.39]), while GSH values remained comparable between Groups 3 and 4. SOD increased significantly in Groups 2-4 (Group 4: 6.25 ng/mL [5.2-7.0]) compared to Group 1 (4.95 ng/mL [3.9-5.6]) (p < 0.001).
CONCLUSION: Although Nintedanib is antifibrotic in pulmonary contexts, it appears to promote penile fibrosis post-IP, likely via excessive VEGFR-2 inhibition, impairing vascular recovery and erectile function. Further studies are needed.