Effects of Losartan, Rapamycin, Doxycycline and Botulinum Toxin A: An Experimentally Induced Urethral Trauma Model in Rats

Purpose To assess the antifibrotic efficacy of losartan, rapamycin, doxycycline, and botulinum toxin A (BTX-A) in an experimentally induced urethral trauma rat model. Methods Sixty male rats were assigned to six groups; sham (n = 10), stricture (n = 10), losartan (n = 10), rapamycin (n = 10), doxycycline (n = 10), and BTX-A (n = 10). The sham group was exposed to only a penoscrotal incision. In the other groups, 10 watt electrocoagulation with a duration of one second was applied at 5 mm intervals to three points on the urethra. Ten units of BTX-A (0.5 ml) was injected into the submucosal tissue following electrocoagulation in the BTX-A group. Losartan (30 mg/kg/day), doxycycline (10 mg/kg/day), and rapamycin (2 mg/kg/day) were administered for 14 days postoperatively by oral gavage to the other three groups. The animals were sacrificed on the 14th days, and their urethral tissues were removed. Results All treatment groups exhibited superiority over the stenosis groups with improvements in fibrosis, inflammation, vascular congestion, epithelial degeneration, and submucosal hemorrhage (p < 0.001). The treatment groups emerged as superior to the stenosis group with decreased interleukin-1β expression (p < 0,001). The mean gene values improved significantly in all treatment groups compared with those in the stenosis group (p < 0.001). Conclusion All treatment groups showed reduced fibrosis. This research is the first to use losartan and doxycycline in urethral stenosis. Further data are needed regarding the use of these drugs for urethral stenosis.