Antifibrogenic role of valproic acid in streptozotocin induced diabetic rat penis

Abstract

We investigated the therapeutic effects of valproic acid (VPA) on erectile dysfunction and reducing penile fibrosis in streptozocin (STZ)-induced diabetic rats. Eighteen male rats were divided into three experimental groups (Control, STZ-DM, STZ-DM plus VPA) and diabetes was induced by transperitoneal single dose STZ. Eight weeks after, VPA and placebo treatments were given according to groups for 15 days. All rats were anesthetised for the measurement of in vivo erectile response to cavernous nerve stimulation. Afterward penes were evaluated histologically in terms of immune labelling scores of endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF) and transforming growth factor-β1 (TGF-β1). Slides were also evaluated in terms of collagen/smooth muscle ratio and penile apoptosis. After the treatment with VPA, erectile responses were found as improved when compared with STZ-DM rats but not statistically meaningful. eNOS and VEGF immune expressions diminished in penile corpora of STZ-DM rats and improved with VPA treatment. VPA led to decrease in TGF-β1 expression and collagen content of diabetic rats' penes. Penile apoptosis was not diminished with VPA. In conclusion, VPA treatment seems to be effective for reducing penile fibrosis in diabetic rats and more prolonged treatment period may enhance erectile functions.

Procedure of Concluding a Contract of the Administration

“…İmtiyaz sözleşmelerinde, sözleşmenin diğer tarafını seçimi hususunda idarenin serbestisinin ve ihtiyarî bir şekilde seçme yetkisinin bulunmadığına yönelik kuralın, imtiyaz sözleşmelerinde geçerli olmadığı 111 ; istisnai olarak idarenin sözleşmeci tarafı seçme serbestisinin tam olduğunun kural olarak kabul edildiği 112 ve rekabet ilkesinin uygulanmasında istisnai durumların varlığının kabul edilebileceği belirtilmektedir 113 .…”