Research Article: Recent Pathophysiological Aspects of Peyronie’s Disease: Role of Free Radicals, Rationale, and Therapeutic Implications for Antioxidant Treatment—Literature Review

Date Published: July 4, 2017

Publisher: Hindawi

Author(s): Gianni Paulis, Gennaro Romano, Luca Paulis, Davide Barletta.

http://doi.org/10.1155/2017/4653512

Abstract

Peyronie’s disease (PD) is a chronic inflammation of tunica albuginea of the corpora cavernosa that causes an inelastic plaque resulting in penis deformation. Although its etiology is not completely known, there is general consensus that PD is genetically transmitted and secondary to penile trauma. In recent years, numerous studies demonstrated the role played by oxidative stress in PD pathogenesis, and other studies have described successful use of antioxidants in PD treatment. Oxidative stress is an integral part of this disease, influencing its progression. In the early stages of PD, the inflammatory infiltrate cells produce high quantities of free radicals and proinflammatory and profibrotic cytokines, with consequent activation of transcription factor NF-κB. While conservative therapies commonly used in the early stages of PD include oral substances (Potaba, tamoxifen, colchicine, and vitamin E), intralesional treatment (verapamil, interferon, steroids, and more recently collagenase clostridium histolyticum-Xiaflex), and local physical treatment (iontophoresis, extracorporeal shock wave therapy, and penile extender), the significant results obtained by emerging treatments with the antioxidants cited in this article suggest these therapeutic agents interfere at several levels with the disease’s pathogenetic mechanisms. Antioxidants therapy outcomes are interesting for good clinical practice and also confirm the fundamental role played by oxidative stress in PD.

Partial Text

Peyronie’s disease (PD), a chronic inflammation of the tunica albuginea of the corpora cavernosa, causes formation of a hard, inelastic plaque, often resulting in penis deformation. Prevalence varies between 3.2% and 13%; it generally affects males around 50 years of age, but recently a rise in frequency has been recorded in younger patients [1, 2]. Like Dupuytren’s contracture, PD more frequently affects white men, more rarely black, and Asian men [3]. Although its etiology is not completely known, there is general consensus that PD is genetically transmitted and secondary to penile trauma [4, 5]. Familiar aggregation and genetic transmission through HLA-B7 antigens had been amply described and understood [6–8]. Recently, a genetic locus that PD shares with Dupuytren’s contracture was identified; WNT2 is the locus involved in genetic predisposition for both Dupuytren’s disease and PD [9]. Previously, some studies had already observed the analogy and strong affinity between the two diseases: Dupuytren’s contracture’s typical cells with “cross-banded” nuclei had been observed in PD plaques in 1976; in 1989, Somers et al., after histological examination of PD plaques, proved an increase in type III collagen content, similarly to what occurs in Dupuytren’s contracture [10, 11].

As can be gathered from the number of references in our article, numerous studies have demonstrated the fundamental role played by oxidative stress in PD pathogenesis, and several studies have described successful use of various antioxidants in PD treatment. Oxidative stress is an integral part of the disease, influencing its progression; in the very early stages of PD, the inflammatory infiltrate cells begin to produce high quantities of ROS and proinflammatory and profibrotic cytokines, with consequent activation of transcription factor NF-κB which induces iNOS production and subsequent release of high nitric oxide radical concentrations. The next chemical reaction cascade leads to production of high amounts of reactive nitrogen species, particularly peroxynitrite, which can damage cells and tissue by lipid peroxidation and DNA fragmentation. As described above, inflammatory cytokine- and NF-κB-induced expression of iNOS leads to overproduction of nitric oxide radical, which reacting with superoxide anion causes peroxynitrite production [34]. Oxidative stress, furthermore, is an important factor in the possible onset of erectile dysfunction in PD, as hyperproduction of superoxide anion and peroxynitrite reduces nitric oxide concentration available for cavernosal muscle relaxation, resulting in long-term endothelial damage; superoxide anion is also reported to have a direct vasoconstriction effect [44, 144]. The presence of high iNOS concentrations has been proven in the cavernous tissue of men with PD [34]. The exact role of iNOS was long unclear, and a number of authors attributed a protective, antifibrotic role to it [39, 145]. Other authors, instead, proved that iNOS inhibition and peroxynitrite scavenging suppressed evolution of the inflammatory response and the normal course of collagen-induced diseases [146, 147]. Moreover, numerous studies listed in our literature review proved that iNOS inhibition after treatment with antioxidants (in PD patients) can have antifibrotic effects, resulting in significant clinical improvement [60–62, 71, 72, 82–89, 95, 128–132].

 

Source:

http://doi.org/10.1155/2017/4653512

 

Leave a Reply

Your email address will not be published.