Effects of ursodeoxycholic acid on erectile dysfunction in diabetic rats

Effects of Ursodeoxycholic Acid on Erectile Dysfunction in Diabetic Rats Erectile dysfunction (ED) which is one of the most common complications of diabetes is a global health problem affecting approximately 75% of men with diabetes. Dysfunction in the NO/cGMP system, which is an important part of erection physiology, corporal tissue fibrosis together with decreased smooth muscle and endothelial cell content in the penis are processes that play a critical role in the pathophysiology of diabetic ED. Many cytokines and growth factors have been reported to contribute to the fibrogenic process in erectile tissue. Transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF) which is activated by TGF-β1 are the main molecules for the induction of the fibrosis. TGF-β1/Smad/CTGF is an important fibrogenic pathway in the pathogenesis of diabetic ED. The aim of the study is to investigate the possible effects of Ursodeoxycholic acid (UDCA), which has been shown to have an antifibrotic effect mediated by TGF-β1/Smad signaling pathway in different tissues, on diabetic penile fibrosis and ED at functional and molecular level. 48 male Spraque Dawley (8-10 weeks) rats were used in the study. After streptozotocin (STZ) induced diabetes, UDCA (20 and 80 mg/kg) or vehicle (saline) was administered by gavage to the rats. Intracavernosal pressure (ICP) and mean arterial pressure (MAP) were measured simultaneously. Maximum-ICP/MAP (m-ICP/MAP) and total-ICP/MAP (t-ICP/MAP) ratios were evaluated as measures of erectile function. In erectile tissue, changes in TGF-β1, fibronectin, pSmad2, Smad2/3, Smad7 and CTGF protein expressions were evaluated by Western blot while histopathological analysis are performed with Masson Trichrome. m-ICP/MAP and t-ICP/MAP were significantly decreased in the diabetic group compared to the control group. Decreased erectile function due to diabetes was significantly prevented with 20 and 80 mg/kg UDCA treatment. While TGF-β1, fibronectin, pSmad2, pSmad2/Smad2 and CTGF expressions increased significantly in the diabetic group compared to the control group, Smad7 levels were significantly decreased. UDCA treatment prevented the increases in those protein expressions dose-dependently; significantly increased Smad7 expression dose-independently. It also significantly prevented STZ-induced cavernosal fibrosis, dose-independently. As a result; UDCA showed a protective effect on STZ-induced penile fibrosis and ED through inhibition of TGF-β1/Smad/CTGF signaling. Keywords: Corpus cavernosum, Diabetes, Fibrosis, Smad