Dipyridamole reduces penile apoptosis in a rat model of post-prostatectomy erectile dysfunction.

Ersagun Karaguzel,Omer Kutlu,Huseyin Eren,Ahmet Alver,Eyup Dil,Ahmet Mentese,Ali Ertan Okatan,Selcuk Kutlu,Ilke Onur Kazaz,Esin Yulug

doi:10.1590/s1677-5538.ibju.2017.0023

Abstract

ABSTRACTPurpose:Despite the nerve-sparing technique, many patients suffer from erectile dysfunction after radical prostatectomy (RP) due to cavernous nerve injury. The aim of this study was to evaluate dipyridamole as a potential treatment agent of post-radical prostatectomy erectile dysfunction.Material and methods:A total of 18 male Sprague-Dawley rats were randomized into three experimental Groups (SHAM+DMSO, BCNI+DMSO and BCNI+DIP). An animal model of bilateral cavernous nerve crush injury (BCNI) was established to mimic the partial nerve damage during nerve-sparing RP. After creating of BCNI, dimethyl sulphoxide (DMSO) was administered transperitoneally as a vehicle to SHAM+DMSO and BCNI+DMSO Groups. BCNI+DIP Group received dipyiridamole (10mg/kg/day) as a solution in DMSO for 15 days. Afterwards, rats were evaluated for in vivo erectile response to cavernous nerve stimulation. Penile tissues were also analyzed biochemically for transforming growth factor-β1 (TGF-β1) level. Penile corporal apoptosis was determined by TUNEL method.Results:Erectile response was decreased in rats with BCNI and there was no significant improvement with dipyridamole treatment. TGF-β1 levels were increased in rats with BCNI and decreased with dipyridamole treatment. Dipyridamole led to reduced penile apoptosis in rats with BCNI and there was no significant difference when compared to sham operated rats.Conclusions:Although fifteen-day dipyridamole treatment has failed to improve erectile function in rats with BCNI, the decline in both TGF-β1 levels and apoptotic indices with treatment may be helpful in protecting penile morphology after cavernous nerve injury.

Highlights

In spite of using the nerve-sparing technique, erectile dysfunction (ED) is a common complication after radical prostatectomy (RP) due to neuropraxia of the cavernous nerve [1]
We aimed to evaluate the effects of daily administration of dipyridamole on penile apoptosis and erectile function measured in vivo in rats with bilateral cavernous nerve crush injury (BCNI)
We investigated the expression of transforming growth factor-β1, a well-known profibrotic cytokine that activates penile fibrosis

Summary

Introduction

In spite of using the nerve-sparing technique, erectile dysfunction (ED) is a common complication after radical prostatectomy (RP) due to neuropraxia of the cavernous nerve [1]. The cavernous nerve regeneration may take several months after surgery and such a lengthy absence of innervations may lead to structural changes within the corpus cavernousum including smooth muscle loss and fibrosis [3, 4]. These changes have been attributed to apoptosis after RP [5, 6]. Some treatment approaches such as phosphodiesterase type 5 (PDE5) inhibitors, erythropoietin, FK506 (tacrolimus) have been tested for preserving the penile vascular bed and functional integrity of the cavernous nerves following RP [3, 8,9,10]. They have proven some benefits for the ability to have sexual intercourse, there is still a need for new treatment approaches to prevent the penile corporeal damage mediated cavernous nerve injury

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