Effects of Astragaloside IV on erectile dysfunction after bilateral cavernous nerve injury

Prostate cancer is one of the most prevalent neoplasia seen in adult men. Injury of cavernous nerves (CN) during radical prostatectomy (RP) performed for resection of tumoral tissue frequently results in erectile dysfunction (ED). ED associated with RP is an iatrogenic complication characterized by penil tissue morphological changes such as cavernosal smooth muscle loss and fibrosis after trauma-induced CN degeneration. TGF-β1/Smads signaling pathway is one of the main mechanisms causing cavernosal fibrosis. The aim of study is to examine the possible therapeutic effects of astragaloside IV (AS-IV), which has been shown antifibrotic properties mediated by TGF-β1/Smads signal inhibition in many tissues, on ED associated with RP using bilateral cavernous nerve injury (BCNI) model. Sprague-Dawley 72 male rats (8-10 weeks) were used in this experiment. Following Sham and BCNI models, the experimental groups were treated with 1 mg/kg/day AS-IV, 5 mg/kg/day AS-IV or vehicle intraperitoneally (i.p.) for 7 and 14 days protocols. At the end of the protocols, intracavernous pressure (ICP) and mean arterial pressure (MAP) were measured simultaneously; maximum-ICP/MAP (m-ICP/MAP) and total-ICP/MAP (t-ICP/MAP) were evaluated as degree of erectile function (EF). While histopathology of cavernosal tissue was examined by masson trichrome method, changes in TGF-β1, fibronectin, pSmad2, Smad2, Smad3 and Smad7 protein expressions levels were evaluated by Western Blot method. In both protocols, m-ICP/MAP and t-ICP/MAP significantly decreased in BCNI groups compared to control groups. 14 days of 1 mg/kg and 5 mg/kg AS-IV treatments was significantly prevented the decrease in EF. TGF-β1, fibronectin, pSmad2 expressions and pSmad2/Smad2 ratio were significantly increased in BCNI groups compared to control groups, however Smad7 levels were significantly decreased. While AS-IV treatment significantly prevented the increase in TGF-β1, fibronectin and the decrease in Smad7 expressions in a dose-dependent manner in both protocols, pSmad2/Smad2 ratio was significantly found to be close to the control only at 5 mg/kg dose. Cavernosal fibrosis induced by BCNI model were significantly hindered by only 14 days of 5 mg/kg AS-IV treatment. As a result, the protective effect of AS-IV on BCNI induced ED is associated with its antifibrotic properties by inhibiting TGF-β1/Smads signal transduction. Keywords: Cavernous nerve injury, Erectile dysfunction, Fibrosis, TGF-β1/Smads