Oxidative stress promotes benign prostatic hyperplasia

Prostate. 2016 Jan;76(1):58-67. doi: 10.1002/pros.23100. Epub 2015 Sep 29.


Background: Benign prostatic hyperplasia (BPH) is characterized by increased tissue mass in the transition zone of the prostate, which leads to obstruction of urine outflow and significant morbidity in the majority of older men. Plasma markers of oxidative stress are increased in men with BPH but it is unclear whether oxidative stress and/or oxidative DNA damage are causal in the pathogenesis of BPH.

Methods: Levels of 8-OH deoxyguanosine (8-OH dG), a marker of oxidative stress, were measured in prostate tissues from normal transition zone and BPH by ELISA. 8-OH dG was also detected in tissues by immunohistochemistry and staining quantitated by image analysis. Nox4 promotes the formation of reactive oxygen species. We therefore created and characterized transgenic mice with prostate specific expression of Nox4 under the control of the prostate specific ARR2PB promoter.

Results: Human BPH tissues contained significantly higher levels of 8-OH dG than control transition zone tissues and the levels of 8-OH dG were correlated with prostate weight. Cells with 8-OH dG staining were predominantly in the epithelium and were present in a patchy distribution. The total fraction of epithelial staining with 8-OH dG was significantly increased in BPH tissues by image analysis. The ARR2PB-Nox4 mice had increased oxidative DNA damage in the prostate, increased prostate weight, increased epithelial proliferation, and histological changes including epithelial proliferation, stromal thickening, and fibrosis when compared to wild type controls.

Conclusions: Oxidative stress and oxidative DNA damage are important in the pathogenesis of BPH.

Keywords: Nox4; benign prostatic hyperplasia; oxidative DNA damage; oxidative stress; transgenic.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Animals
  • DNA Damage
  • Deoxyguanosine / analogs & derivatives*
  • Deoxyguanosine / metabolism
  • Epithelium* / metabolism
  • Epithelium* / pathology
  • Humans
  • Immunohistochemistry
  • Male
  • Mice, Transgenic
  • NADPH Oxidase 4
  • NADPH Oxidases / metabolism
  • Oxidative Stress / genetics
  • Prostate* / metabolism
  • Prostate* / pathology
  • Prostatic Hyperplasia* / metabolism
  • Prostatic Hyperplasia* / pathology
  • Statistics as Topic
  • Tumor Burden


  • 8-Hydroxy-2'-Deoxyguanosine
  • NADPH Oxidase 4
  • NADPH Oxidases
  • NOX4 protein, human
  • Deoxyguanosine