Oxidative stress promotes benign prostatic hyperplasia

Abstract

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.

Oxidative stress before and after surgery in benign prostatic hyperplasia patients

“…Additionally, increased urine 8‐OhdG level was reported in rabbits with partial bladder outlet obstruction (Lin et al, ). Vital et al have determined increased 8‐OH dG in normal transition zone and BPH tissues in prostates harvested from transgenic mice (Nox4) compared with wild‐type littermate controls (Vital, Castro, & Ittmann, ). In their transgenic mouse model in which Nox4 expressed in prostatic epithelium resulted in increased oxidative DNA damage correlating well with the increased prostate weight, and epithelial proliferation supporting the hypothesis that oxidative stress plays a causal role in BPH (Vital et al, ).…”

“…Vital et al have determined increased 8‐OH dG in normal transition zone and BPH tissues in prostates harvested from transgenic mice (Nox4) compared with wild‐type littermate controls (Vital, Castro, & Ittmann, ). In their transgenic mouse model in which Nox4 expressed in prostatic epithelium resulted in increased oxidative DNA damage correlating well with the increased prostate weight, and epithelial proliferation supporting the hypothesis that oxidative stress plays a causal role in BPH (Vital et al, ). DNA damage could have caused point mutations, deletions or rearrangements, thus affecting apoptosis leading to hyperplastic or precancerous transformation in prostate gland (Hamid, Umbas, & Mochtar, ).…”

343 The Anti-Inflammatory and Anti-Microbial Effects of the Novel Herbal Formulation (WSY-1075) on Chronic Bacterial Prostatitis Rat Model

“…Excessive free radicals and reactive oxygen species can interact directly with and damage DNA [25]. Increased oxidative DNA damage is also present in BPH and plays a role in tissue proliferation [26].…”

Oxidative stress and its possible relation to lower urinary tract functional pathology

“…Plasma markers of oxidative stress are increased in men with BPH, but it is unclear whether oxidative stress and/or oxidative DNA damage are causative in the pathogenesis of BPH. Vital et al measured levels of 8‐OHdG in prostate tissues from normal transition zone or hyperplastic transition zone (BPH) taken from radical prostatectomies. 8‐OHdG was also detected in tissues by immunohistochemistry and staining quantitated by image analysis.…”