Rapamycin Inhibits Formation of Urethral Stricture in Rabbits

Abstract

Rapamycin has been reported to inhibit hepatic fibrosis, lung fibrosis, renal fibrosis, and subglottic stenosis. Fibrosis is also involved in urethral stricture. Therefore, we investigated the effect of rapamycin on the inhibition of urethral stricture formation in a rabbit model. First, models of urethral stricture were successfully established by electrocoagulation of the bulbar urethra in adult New Zealand male rabbits. Forty-six model rabbits were randomly assigned to four groups: high-dose rapamycin (R H , 1.0 mg/day), low-dose rapamycin (R L , 0.1 mg/ day), dimethyl sulfoxide (DMSO) alone (DMSO, solvent control), and normal saline (NS). Urethral stricture was assessed by a retrograde urethrogram and video-urethroscopy. Urethra pathology was evaluated by hematoxylin and eosin and Sirius red staining. After 28 days of treatment, lumen reduction in the R H , R L , DMSO, and NS groups was 36.0, 56.5, 69.1, and 82.9, respectively. Comparison of the rapamycin groups (R H and R L ) and control groups (DMSO and NS) indicated significantly less restriction in the rapamycin groups. Histopathological analysis confirmed the presence of fibroblasts and an increase in collagen at the stricture site in the two control groups but not in the R H or R L groups. These results indicate that rapamycin inhibits experimentally induced urethral stricture formation in rabbits. This effect may be due to its inhibition of fibroblast proliferation and collagen expression.

Effect of Mitomycin, Bevacizumab, and 5-Fluorouracil to Inhibit Urethral Fibrosis in a Rabbit Model

“…21 In another study, rapamycin was shown to be effective for inhibiting fibroblast proliferation and collagen expression. 20 Both experimental studies showed that inhibition of fibroblast proliferation and collagen expression is critical for preserving the patency of the urethral lumen. In the present study, we used similar criteria to assess the efficacy of MMC, bevacizumab, and 5-FU.…”

“…Therefore, experimental and clinical studies have been performed to explore the efficacies of different molecules for preventing US formation. [20][21][22] Metalloproteinase-1 is another agent that has been used in an attempt to alleviate US after urethral injury. In one study, metalloproteinase-1 reportedly induced a lower collagen concentration in the traumatized region of the experimental group than the control group, and the researchers concluded that it contributed to the maintenance of urethral patency.…”

An Experimental Model of Urethral Stricture in Rabbits Using Holmium Laser under Urethroscopic Direct Visualization

“…The male rabbit urethra, composed of epithelium and corpus spongiosum, has similar histological morphology and structure to that of humans [7,14,15]. Furthermore, the urethra of the adult male rabbit is 5-7 cm long, with a lumen diameter similar to that of a human infant [14], making it suitable for pediatric urethroscope manipulation.…”

Docetaxel Inhibits Urethral Stricture Formation, an Initial Study in Rabbit Model

“…As described by Chong [12], meglumine amine (380 g/L) was used as contrast medium, which was slowly and directly injected into the urethra under X-ray monitoring. Retrograde urethrography was continued until urethral lumen was manifested well.…”

“…In the near decades, it is widely confirmed that rapamycin and paclitaxel eluting stent showed a satisfactory inhibiting effect on restenosis of coronary artery [10], [11]. And our previous study had exposed rapamycin could inhibit urethral stricture formation in rabbits [12]. In this study, the role of docetaxel, a semi-synthetic analogue of paclitaxel, on inhibition of urethral stricture formation was investigated.…”