Abstract

There is an unmet need for treatment of erectile dysfunction resulting from radical prostatectomy and cavernous nerve (CN) injury. Given the neuroprotective properties of docosahexaenoic acid (DHA), we investigated its effect on penile functional and structural recovery in a rat model of bilateral cavernous nerve injury. Rats were subject to CN injury and received intraperitoneal administration of either vehicle or a DHA nanoemulsion (nano-DHA) at 10, 50, or 250 μg/kg. Functional testing and histological analyses were performed at 28 days post-injury. The maximum intracavernosal pressure (ICP) and other measures of erectile function were significantly higher in the nano-DHA groups than in the vehicle group (p < 0.05). The ratio of area of expression of neuronal nitric oxide synthase (nNOS)/β-III tubulin, numbers of axon and smooth muscle cell content were significantly higher in the 50 μg/kg nano-DHA group than in the vehicle group (p < 0.05). A qualitative increase in the smooth muscle cells/collagen ratio and decrease in apoptosis was observed in the nano-DHA groups relative to the vehicle group: however, these differences were not statistically significant. Our data demonstrate that nano-DHA, particularly the 50 μg/kg regimen, improves erectile function after bilateral CN injury in rats by neuroprotection and other anti-fibrotic and anti-apoptotic mechanisms.

Highlights

  • There is an unmet need for treatment of erectile dysfunction resulting from radical prostatectomy and cavernous nerve (CN) injury

  • The area under the curve (AUC) for intracavernosal pressure (ICP) and ∆ICP/mean arterial pressure (MAP) measures and the maximum ICP/MAP values were significantly higher for all nano-docosahexaenoic acid (DHA) groups and the sham group than those for the vehicle group (p < 0.05 for all comparisons)

  • We found that treatment with nano-DHA resulted in the recovery of erectile function as defined by increases in ICP, MAP, and other functional measures

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Summary

Introduction

There is an unmet need for treatment of erectile dysfunction resulting from radical prostatectomy and cavernous nerve (CN) injury. Given the neuroprotective properties of docosahexaenoic acid (DHA), we investigated its effect on penile functional and structural recovery in a rat model of bilateral cavernous nerve injury. The ratio of area of expression of neuronal nitric oxide synthase (nNOS)/β-III tubulin, numbers of axon and smooth muscle cell content were significantly higher in the 50 μg/kg nano-DHA group than in the vehicle group (p < 0.05). Normal erectile function following nerve-sparing radical prostatectomy is only 20–25%, and these rates have not improved over the last 17 years[1]. We aimed to characterize the effect and appropriate dosage of nanoemulsion (nano)-DHA in a rat model of bilateral CN injury and erectile dysfunction. We investigated the effect of 3 regimens of nano-DHA (10 μg/kg, 50 μg/kg, and 250 μg/kg) on functional and structural changes in the corpus cavernosum (CC) and CNs

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