title: Role of oxidative stress in a rat model of radiation-induced erectile dysfunction.
abstract: BACKGROUND
  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. Aims.  To investigate role of oxidative stress after prostate-confined irradiation in a rat model of radiation-induced ED.
  
  
  METHODS
  Fifty-four 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.
  
  
  METHODS
  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 gp91(phox)), markers of oxidative DNA damage (8-hydroxy-2'-deoxyguanosine [8-OHdG]), lipid peroxidation (4-hydroxynonenal [4HNE]), and inflammatory response including inducible nitric oxide synthase, macrophage activation (ED-1), and nitrotyrosine, 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. Increased expression of Nox4, gp91(phox), 8-OHdG, and 4HNE were observed in the prostate and CC after RT. Similarly, expressions of inflammatory markers were significantly increased. There was a trend for increased Nrf2 after 4 weeks. ICP/MAP ratio negatively correlated with higher expression level of oxidative markers.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Urologic Surgery, Department of Surgery and Duke Prostate Center, Duke University Medical Center, Durham, NC, USA. masaki.kimura228@gmail.com
authors.forename: Masaki
authors.initials: M
authors.lastname: Kimura
authors.forename: Zahid N
authors.initials: ZN
authors.lastname: Rabbani
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Zodda
authors.forename: Hui
authors.initials: H
authors.lastname: Yan
authors.forename: Isabel L
authors.initials: IL
authors.lastname: Jackson
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Polascik
authors.forename: Craig F
authors.initials: CF
authors.lastname: Donatucci
authors.forename: Judd W
authors.initials: JW
authors.lastname: Moul
authors.forename: Zeljko
authors.initials: Z
authors.lastname: Vujaskovic
authors.forename: Bridget F
authors.initials: BF
authors.lastname: Koontz
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D007172:Erectile Dysfunction / Q000209:etiology / Q000503:physiopathology*; D007249:Inflammation / Q000378:metabolism; D008297:Male; D016555:Matched-Pair Analysis; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress; D010410:Penile Erection; D010413:Penis / Q000378:metabolism / Q000503:physiopathology; D011467:Prostate / Q000378:metabolism / Q000503:physiopathology; D011471:Prostatic Neoplasms / Q000532:radiotherapy; D011833:Radiation Injuries, Experimental / Q000503:physiopathology*; D011878:Radiotherapy / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015415:Biomarkers; D019255:NADPH Oxidases