ABSTRACT
Pomegranate (POM) juice may benefit the erectile process, but the scientific evidence is lacking. This study evaluates the molecular characterisation and confirmation of POM's action on human corpus cavernosum (HCC) obtained from patients (n = 16) undergoing penile prosthesis implantation. After phenylephrine contraction, the relaxant effects of POM with various inhibitors in the presence and absence of palmitic acid (PA)-induced acute oxidative stress were investigated. Electrical field stimulation (EFS)- and acetylcholine (ACh)-induced relaxation were performed using organ bath preparation. Expression of neuronal nitric oxide synthase (nNOS), endothelial (eNOS), phosphodiesterase (PDE)-5A and cGMP levels were assessed in cells from ex vivo organ cultures of HCC, using RT-PCR, ELISA and immunohistochemistry techniques. POM induced marked relaxation of HCC (maximum response: 97.0 ± 3.1%) and reversed the PA-induced decrease of EFS (20 Hz). nNOS transcription was increased by 7-fold in POM-treated cells without influencing eNOS and PDE5A expressions. We conclude that POM induced marked relaxation of HCC via: (i) nNOS stimulation, and (ii) downstream relaxation stimulated by nNOS and cGMP and bypassing the NO and PDE5. This action provides a rationale for the therapeutic or preventative use of POM in men with erectile dysfunction who do not respond well to PDE5 inhibitors.
Subject(s)
Antioxidants/pharmacology , Fruit and Vegetable Juices , Lythraceae , Muscle, Smooth, Vascular/drug effects , Oxidative Stress/drug effects , Penis/drug effects , Cyclic GMP/metabolism , Humans , Male , Nitric Oxide Synthase Type I/metabolism , Nitric Oxide Synthase Type III/metabolism , Phenylephrine/pharmacology , Vasoconstrictor Agents/pharmacologyABSTRACT
Peyronie's disease (PD) is a localized connective tissue disorder that involves the tunica albuginea (TA) of the penis. While surgical correction remains the gold standard, the search for an effective and less invasive therapy continues. The objective of this study was to evaluate the effects of intratunical injection of adipose tissue-derived stem cells (ADSCs) for the prevention and treatment of erectile dysfunction in a rat model of PD. Twenty-four male Sprague-Dawley rats (300-350 g) were randomly divided into four groups: sham, PD, PD + ADSC (prevention) and PD + ADSC (treatment). All rats underwent penile injections into the TA with 50 µL vehicle (sham) or 0.5 µg transforming growth factor (TGF)-ß1 (remaining groups). The ADSC groups received intratunical injections with 0.5 million rat-labelled ADSCs on day 0 (prevention) or day 30 (treatment). Forty-five days following TGF-ß1 injection, rats underwent cavernous nerve stimulation (CNS) with total intracavernous-to-mean arterial pressure ratio (ICP/MAP) and total ICP recorded to measure response to therapy. Tissues were evaluated histologically and for mRNA expression of tissue inhibitors of metalloproteinases (TIMPs), matrix metalloproteinases (MMPs) and zymographic activity of MMPs. Statistical analysis was performed by analysis of variance followed by the Tukey test for post hoc comparisons. In both prevention and treatment groups, intratunical injection of ADSCs resulted in significantly higher ICP/MAP and total ICP in response to CNS compared with the PD group. Local injection of ADSCs prevented and/or reduced Peyronie's-like changes by decreasing the expression of TIMPs, and stimulating expression and activity of MMPs. This study documents the preventive and therapeutic benefits of ADSC on penile fibrosis and erectile function in an animal model of PD.
