1003 ROLE OF OXIDATIVE STRESS IN A RAT MODEL OF RADIATION-INDUCED ERECTILE DYSFUNCTION

Abstract

You have accessJournal of UrologySexual Function/Dysfunction/Andrology: Basic Research II1 Apr 20121003 ROLE OF OXIDATIVE STRESS IN A RAT MODEL OF RADIATION-INDUCED ERECTILE DYSFUNCTION Masaki Kimura, Zahid Rabbani, Andrew Zodda, Hui Yan, Isabel Jackson, Thomas Polascik, Craig Donatucci, Judd Moul, Zeljko Vujaskovic, and Bridget Koontz Masaki KimuraMasaki Kimura Durham, NC More articles by this author , Zahid RabbaniZahid Rabbani Durham, NC More articles by this author , Andrew ZoddaAndrew Zodda Durham, NC More articles by this author , Hui YanHui Yan Durham, NC More articles by this author , Isabel JacksonIsabel Jackson Durham, NC More articles by this author , Thomas PolascikThomas Polascik Durham, NC More articles by this author , Craig DonatucciCraig Donatucci Durham, NC More articles by this author , Judd MoulJudd Moul Durham, NC More articles by this author , Zeljko VujaskovicZeljko Vujaskovic Durham, NC More articles by this author , and Bridget KoontzBridget Koontz Durham, NC More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.1105AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Chronic oxidative stress is one of the major factors playing an important role in radiation-induced normal tissue injury. However, the role of oxidative stress in radiation-induced erectile dysfunction (ED) has not been fully investigated. In present study, we aim to investigate role of oxidative stress after prostate-confined irradiation in a rat model of radiation-induced ED. METHODS 54 young adult male rats (10-12 weeks of age) were divided into age-matched sham radiotherapy (RT) and RT groups. Irradiated animals received prostate confined radiation in a single 20 Gy fraction. Intracavernous pressure (ICP) measurements with cavernous nerve electrical stimulation were conducted at 2, 4, and 9 weeks following RT. The protein expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits (Nox4 and gp91phox), markers of oxidative DNA damage (8-OHdG), lipid peroxidation (4HNE), and inflammatory response including inducible nitric oxide synthase (iNOS), macrophage activation (ED-1), and nitrotyrosine (NT), and endogenous antioxidant defense by nuclear factor erythroid 2-related factor (Nrf2) were evaluated in irradiated prostate tissue and corpora cavernosa (CC). In addition, we investigated the relationships between results of ICP/ mean arterial pressure (MAP) ratios and expression level of oxidative stress markers. RESULTS In the RT group, hemodynamic functional studies demonstrated a significant time-dependent decrease in ICP. Protein expression of Nox4, gp91phox, 8-OHdG, and 4HNE were increased in the prostate and CC after RT. Similarly, expressions of inflammatory markers were significantly increased in the both tissues. There was a trend for increased Nrf2 after 4 weeks in CC. ICP/MAP ratio negatively correlated with higher expression level of oxidative markers. CONCLUSIONS Current data show time-dependent physiological EF impairment occurs following prostate-confined stereotactic RT with extremely low toxicity. NADPH oxidase activation and chronic oxidative stress were observed in irradiated prostate tissue and CC, which correlated with lower ICP/MAP ratio. Persistent inflammatory responses were also found in both tissues after RT. These findings suggest that oxidative stress plays a crucial role in the development of radiation-induced ED. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e408 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Masaki Kimura Durham, NC More articles by this author Zahid Rabbani Durham, NC More articles by this author Andrew Zodda Durham, NC More articles by this author Hui Yan Durham, NC More articles by this author Isabel Jackson Durham, NC More articles by this author Thomas Polascik Durham, NC More articles by this author Craig Donatucci Durham, NC More articles by this author Judd Moul Durham, NC More articles by this author Zeljko Vujaskovic Durham, NC More articles by this author Bridget Koontz Durham, NC More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...