Effect of icariin in combination with daily sildenafil on penile atrophy and erectile dysfunction in a rat model of bilateral cavernous nerves injury

Abstract

The commonly utilized phosphodiesterase type 5 inhibitors do not lead to satisfactory penile erection after radical prostatectomy mainly because of insufficient nitric oxide drive from the damaged cavernous nerves. The aim of this study was to assess the efficacy and mechanisms of icariin in combination with daily sildenafil on neurogenic erectile dysfunction and penile atrophy in a rat model of bilateral cavernous nerves injury. Sixty male Sprague-Dawley rats injected with 5-ethynyl-2-deoxyuridine (50 mg/kg) at postnatal day 1 for the purpose of tracking endogenous stem cells in penis. Forty-eight rats of bilateral cavernous nerves injury were randomized equally into gavage feeding of vehicle, sildenafil (10 mg/kg), icariin (1.5 mg/kg) and sildenafil + icariin, respectively. Twelve sham-operated rats served as control. The intracavernous pressure and mean arterial pressure was measured and mid-penile cross sections were histologically examined 5 weeks after surgery. Western blotting of cavernous tissue protein was also performed. Animals treated with sildenafil + icariin had significantly higher mean intracavernous pressure/mean arterial pressure ratio relative to other rats with bilateral cavernous nerves injury (p < 0.05). The circumference and mean cross-sectional area of the paired corpus cavernosum were effectively preserved in the sildenafil + icariin. Treatment with sildenafil + icariin significantly increased the cavernous cyclic guanosine monophosphate concentration compared with the icariin group (p < 0.05). In addition, the numbers of neuronal nitric oxide synthase-positive nerves and 5-ethynyl-2-deoxyuridine-positive cells co-expressing S100 in the icariin-treated groups were greater compared with the bilateral cavernous nerves injury control group (p < 0.05). These data suggest that the combined use of icariin and daily sildenafil holds promise as a potential therapy for neurogenic erectile dysfunction in the future. The underlying mechanisms appears to involve two aspects: (i) icariin promotes differentiation of endogenous stem cells to Schwann cells, which help to repair the damaged neural pathway for erection; (ii) on this basis, sildenafil can further improve penile engorgement through the cyclic guanosine monophosphate-dependent smooth muscle relaxation.

Enhanced effects of salidroside on erectile function and corpora cavernosa autophagy in a cavernous nerve injury rat model

“…In this study, for our ICP experiment, we assessed related parameters, such as maximum ICP, the maximum ICP/MAP ratio, and the slope of maximum ICP, 3 weeks after the modelling operation and showed that the administration of either salidroside or rapamycin can ameliorate ED in rats suffering from BCNI. CN‐injured ED leads to atrophy due to long‐term hypoxia and fibrotic deposition (Xu et al., 2017), and the penile tissue weight/body weight ratio in the M group was similar to the previous results. Meanwhile, results indicated that both salidroside and rapamycin treatment maintained the penile index and the area of the CC compared to those in the M group.…”

Intracavernous injection of size-specific stem cell spheroids for neurogenic erectile dysfunction: Efficacy and risk versus single cells

“…Twelve SD rats were randomly assigned to the sham group (i.e., exposing and isolating CNs, without crushing CNs) and received an ICI of 0.2 ml phosphate buffer solution (PBS). In the other 120 rats, the CNs were isolated and crushed bilaterally using a microsurgical needle holder [18]. On the same day of surgery, the rats that underwent bilateral CNs injury were randomly divided into three groups: those who received an ICI of 0.2 ml PBS (n = 24 animals), free ADSCs suspension (abbreviated to FAs, 0.5 £ 10 6 , 1 £ 10 6 , 2 £ 10 6 and 4 £ 10 6 cells in 0.2 ml PBS, n = 12 animals per dose), or ADSCs-based spheroids (abbreviated to ASs, 500, 1000, 2000 and 4000 ASs in 0.2 ml PBS, 1 £ 10 3 ADSCs per spheroid, n = 12 animals per group).…”

Tirotoksikoz nedenli erektil disfonksiyon üzerine sildenafil etkisinin histopatolojik olarak değerlendirilmesi

“…Sıçan penis dokusunda reaktif oksijen türlerinin (ROS) aşırı üretiminin erektil disfonksiyon gelişiminde önemli bir rol oynadığı gösterilmiştir (28,29). Süperoksit anyonu hızla NO'yu inaktive eder, kavernozal düz kasları gevşetme yeteneğini bozar (30) (39). Özden ve arkadaşlarının yaptığı bir çalışmada da unilateral ve bilateral kavernöz sinir hasarı yapılan sıçanlarda sildenafil tedavisinin penil ağırlık üzerine olumlu etkileri olduğu görülmüş, TUNEL ile düz kaslarda apoptoza giden hücre sayısında bilateral sinir hasarı yapılan grupta artış olduğu ve sildenafil uygulamasının apoptozu önleme yönünde olumlu etkileri olduğu ortaya konmuştur (40).…”