No abstract

No 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.

IntroductionUrethral stricture, a frequent source of lower urinary tract disorders in men, is still a difficult problem for urologists. Based the anti-restenosis effect of paclitaxel on coronary artery, the role of docetaxel, a semi-synthetic analogue of paclitaxel, in limiting urethral stricture formation was studied.MethodsForty adult New Zealand male rabbits were involved in this study, which were randomly assigned into 3 groups, namely a high dose docetaxel (DH, 0.1 mg/d), a low dose docetaxel (DL, 0.01 mg/d) and a control (C) group, with 16, 16, 8 rabbits in each group, respectively. All animals underwent a 10 mm-long circumferential electrocoagulation of the bulbar urethra with a 13Fr pediatric resectoscope. Drugs were given by urethral irrigation daily and continuous for 28 days. Stricture formation was assessed by retrograde urethrography and videourethroscopy. Urethra pathology was evaluated by hematoxylin and eosin staining and Sirius red staining.ResultsAt the end of this study, 15, 14 and 7 rabbits remained for evaluation in DH, DL and C group, respectively. Urethral diameters in DH, DL and C group were (7.17±1.63) mm, (6.55±0.62) mm, (3.23±1.36) mm, with a normal urethral diameter of (9.08±1.29) mm. Lumen reduction in DH, DL and C group were (36.93±11.58)%, (48.03±7.89)% and (84.66±14.95)%, respectively. Statistically difference could be found between every two groups (p<0.05) both in urethral diameters and in lumen reduction, except for compare of urethral diameters between DH and DL group. Histological examination confirmed mass fibrous tissue and collagen content at the stricture sit in C group, whereas less in docetaxel treated rabbits.ConclusionsDocetaxel could limit urethral stricture formation, which may be due to inhibition of fibrous tissue and collagen expression. Docetaxel may become a new choice in the prevention of urethral stricture formation.

Di-(2-ethylhexyl) phthalate (DEHP) is the most widely used plastizer in the world and can suppress testosterone production via activation of oxidative stress. Genistein (GEN) is one of the isoflavones ingredients exhibiting weak estrogenic and potentially antioxidative effects. However, study on reproductive effects following prepubertal multiple endocrine disrupters exposure has been lacking. In this study, DEHP and GEN were administrated to prepubertal male Sprague-Dawley rats by gavage from postnatal day 22 (PND22) to PND35 with vehicle control, GEN at 50 mg/kg body weight (bw)/day (G), DEHP at 50, 150, 450 mg/kg bw/day (D50, D150, D450) and their mixture (G + D50, G + D150, G + D450). On PND90, general morphometry (body weight, AGD, organ weight, and organ coefficient), testicular redox state, and testicular histology were studied. Our results indicated that DEHP could significantly decrease sex organs weight, organ coefficient, and testicular antioxidative ability, which largely depended on the dose of DEHP. However, coadministration of GEN could partially alleviate DEHP-induced reproductive injuries via enhancement of testicular antioxidative enzymes activities, which indicates that GEN has protective effects on DEHP-induced male reproductive system damage after prepubertal exposure and GEN may have promising future in its curative antioxidative role for reproductive disorders caused by other environmental endocrine disruptors.