Akademik Veri Yönetim Sistemi
INTERNATIONAL JOURNAL OF IMPOTENCE RESEARCH, cilt.36, sa.8, ss.886-895, 2024 (SCI-Expanded)
Corporal tissue fibrosis is critical in diabetes-associated erectile dysfunction. Transforming growth factor-beta 1/Small mothers against decapentaplegic-2 (TGF-beta 1/Smad2) contributes to the induction of fibrosis in corporal tissue. Smad7 is accepted as a general negative regulator of Smad signaling, although its role in corporal fibrosis is unknown. Ursodeoxycholic acid (UDCA) is a hydrophilic bile acid used for biliary and liver related disorders and has antifibrotic effects in the liver. This study investigated the effects of UDCA on diabetic erectile dysfunction. Forty-eight male Spraque Dawley rats were divided into six groups: nondiabetic (n=6), nondiabetic+20mg/kg UDCA (n=6), nondiabetic+80mg/kg UDCA (n=6), diabetic (n=10), diabetic+20mg/kg UDCA (n=10), diabetic+80mg/kg UDCA (n=10). Diabetes was induced by intraperitoneal injection of 60mg/kg Streptozocin. UDCA (20 and 80mg/kg/day) or saline was subsequently administered via oral gavage for 56 days. Erectile function was evaluated as measurement of maximum intracavernosal pressure (m-ICP)/mean arterial pressure (MAP) and total ICP/MAP. Corporal tissues were evaluated by Western blotting and Masson's trichrome staining. Electrical stimulation-induced m-ICP/MAP responses were higher in UDCA-treated diabetic rats compared to untreated diabetic rats, respectively (20mg/kg; 4V: 0.77 +/- 0.11 vs 0.45 +/- 0.09, p=0.0001 and 80mg/kg; 4V: 0.78 +/- 0.11 vs 0.45 +/- 0.09, p=0.0001) UDCA prevented the increase in phospho-Smad2 and fibronectin protein expressions in diabetic corporal tissue both at 20mg/kg (p=0.0002, p=0.002 respectively) and 80mg/kg doses (p<0.0001 for both). Smad7 protein expressions were significantly increased in the UDCA-treated diabetic groups compared to the untreated diabetic group (20mg/kg: p=0.0079; 80mg/kg: p=0.004). Furthermore, UDCA significantly prevented diabetes-induced increase in collagen (20mg/kg: p=0.0172; 80mg/kg: p=0.0003) and smooth muscle loss (20mg/kg: p=0.044; 80mg/kg: p=0.039). In conclusion, UDCA has a potential protective effect on erectile function in diabetic rats by altering fibrotic pathways via inhibition of TGF-beta 1/Smad2 and activation of Smad7.