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Oxidative stress promotes benign prostatic hyperplasia
Author(s) -
Vital Paz,
Castro Patricia,
Ittmann Michael
Publication year - 2016
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.23100
Subject(s) - oxidative stress , prostate , hyperplasia , nox4 , pathogenesis , endocrinology , medicine , chemistry , pathology , cancer , nadph oxidase
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. Prostate 76:58–67, 2016 . © 2015 Wiley Periodicals, Inc.