Antioxidative effect of hydroalcoholic extracts of fruit and pit of Elaeagnud angosifolia against oxidative stress markers in benign prostatic hyperplasia

BackgroundProstate cancer (PCa) and benign prostatic hyperplasia (BPH) are diseases of elderly men and are related to increased oxidative stress (OS). Although prolidase has a role in collagen metabolism, it is also used to evaluate OS in many diseases. However, there is a lack of data about serum prolidase activity (SPA) in prostate cancer. The aim of this study was to evaluate and compare SPA levels in males with BPH and PCa.MethodsEvaluation was made of a total of 81 men who underwent transrectal ultrasound guided prostate biopsy for a definitive diagnosis due to high PSA levels. Patients were separated into 2 groups as BPH and PCa patients. Pre-biopsy malondialdehyde (MDA), superoxide dismutase (SOD), PSA levels and serum prolidase activities (SPA) were compared between the groups and the correlations of SPA with the other parameters were also investigated in both groups.ResultsBPH was diagnosed in 51 patients and PCa in 30. The mean age of patients was similar in both groups as 63.25 ± 5.81 years in the BPH group 65.30 ± 7.35 years in the PCa group(p:0.081). The median MDA and SOD levels were insignificantly increased in the PCa patients. SPA values were similar in BPH and PCa patients. SPA did not correlate with age, PSA, MDA or SOD levels in either group.ConclusionsOur study results revealed that serum prolidase activity is similar in BPH and PCa cases and is not correlated with MDA, SOD or PSA levels.

Association of glutathione S-transferase (GST) M1 and T1 deletions with benign prostate hyperplasia (BPH) and prostate cancer is well reported. These enzymes metabolize numerous toxins thus protecting from oxidative injury. Oxidative stress has been associated with development of BPH and prostate cancer. The present study was designed to analyze role of GST deletions in development of oxidative stress in these subjects. GSTs are responsible for metabolism of toxins present in tobacco therefore effect of tobacco usage in study groups was also studied. Three groups of subjects: BPH (57 patients), prostate cancer (53 patients) and controls (46 subjects) were recruited. Genotyping was done using a multiplex polymerase chain reaction (PCR) method. Malondialdehyde (MDA) levels as marker of oxidative stress were estimated by measuring thiobarbituric acid reactive substance (TBARS) in plasma. Based on genotyping, subjects were categorized into: GSTM1+/GSTT1+, GSTM1-/GSTT1+, GSTM1+/GSTT1- and GSTM1-/GSTT1-. Significantly higher plasma MDA levels were noticed in GSTM1-/GSTT1- as compared to GSTM1+/GSTT1+ in all study groups. Double deletion (GSTM1-/GSTT1-) is associated with higher oxidative stress which might play a role in the pathogenesis of BPH and prostate cancer. However, other markers of oxidative stress should be analyzed before any firm conclusion.

Association of glutathione S-transferase (GST)M1andT1deletions with benign prostate hyperplasia (BPH) and prostate cancer is well reported. These enzymes metabolize numerous toxins thus protecting from oxidative injury. Oxidative stress has been associated with development of BPH and prostate cancer. The present study was designed to analyze role ofGSTdeletions in development of oxidative stress in these subjects. GSTs are responsible for metabolism of toxins present in tobacco therefore effect of tobacco usage in study groups was also studied. Three groups of subjects: BPH (57 patients), prostate cancer (53 patients) and controls (46 subjects) were recruited. Genotyping was done using a multiplex polymerase chain reaction (PCR) method. Malondialdehyde (MDA) levels as marker of oxidative stress were estimated by measuring thiobarbituric acid reactive substance (TBARS) in plasma. Based on genotyping, subjects were categorized into:GSTM1+/GSTT1+, GSTM1-/GSTT1+, GSTM1+/GSTT1- and GSTM1-/GSTT1-. Significantly higher plasma MDA levels were noticed inGSTM1-/GSTT1- as compared toGSTM1+/GSTT1+in all study groups. Double deletion (GSTM1-/GSTT1-) is associated with higher oxidative stress which might play a role in the pathogenesis of BPH and prostate cancer. However, other markers of oxidative stress should be analyzed before any firm conclusion.

Personalized Medicine for the Management of Benign Prostatic Hyperplasia

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

Benign prostatic hyperplasia (BPH) is a common disease in elderly men with uncertain molecular mechanism, and oxidative stress (OS) has also been found associated with BPH development. Recently, we found that prostate-associated gene 4 (PAGE4) was one of the most significantly changed differentially expressed genes (DEGs) in BPH, which can protect cells against stress stimulation. However, the exact role of PAGE4 in BPH remains unclear. This study is aimed at exploring the effect of PAGE4 in BPH under OS. Human prostate tissues and cultured WPMY-1 and PrPF cells were utilized. The expression and localization of PAGE4 were determined with qRT-PCR, Western blotting, and immunofluorescence staining. OS cell models induced with H2O2 were treated with PAGE4 silencing or PAGE4 overexpression or inhibitor (N-acetyl-L-cysteine (NAC)) of OS. The proliferation activity, apoptosis, OS markers, and MAPK signaling pathways were detected by CCK-8 assay, flow cytometry analysis, and Western blotting. PAGE4 was shown to be upregulated in human hyperplastic prostate and mainly located in the stroma. Acute OS induced with H2O2 increased PAGE4 expression (which was prevented by OS inhibitor), apoptosis, cell cycle arrest, and reactive oxygen species (ROS) accumulation in WPMY-1 and PrPF cells. siPAGE4 plus H2O2 potentiated H2O2 effect via reducing the p-ERK1/2 level and increasing p-JNK1/2 level. Consistently, overexpression of PAGE4 offset the effect of H2O2 and partially reversed the PAGE4 silencing effect. However, knocking down and overexpression of PAGE4 alone determined no significant effects. Our novel data demonstrated that augmented PAGE4 promotes cell survival by activating p-ERK1/2 and decreases cell apoptosis by inhibiting p-JNK1/2 under the OS, which could contribute to the development of BPH.

Sex hormones and oxidative stress mediated phthalate-induced effects in prostatic enlargement

Protocatechuic acid (PA) is a polyphenol-recognized for its efficacy as an antioxidant-possesses anticancer, anti-inflammatory, antioxidant properties. The efficacy of PA in the management of benign prostatic hyperplasia (BPH) has not been investigated. Forty-two castrated rats (n = 7) were treated as follows: control (corn oil), BPH only received testosterone propionate (TP) (TP 3 mg/kg intraperitoneally), BPH + PA (TP 3 mg/kg + PA 40 mg/kg), BPH + finasteride (Fin) (TP 3 mg/kg + Fin 10 mg/kg), PA only (40 mg/kg: by gavage), and Fin only (10 mg/kg: by gavage) for 4 weeks. In BPH rats, there were significant (P < .05) increases in prostatic (250%) and organosomatic (280%) weights compared with controls. Cotreatment decreased prostatic weights by 19% (PA) and 21% (Fin). Markers of inflammation: myeloperoxidase activities increased in serum (148%) and prostate (70%), as well as nitric oxide levels serum (92%) and prostatic (95%). Proinflammatory cytokines interleukin-1β and tumor necrosis factor-α increased by 3.6- and 2.8-fold. Furthermore, prostatic malondialdehyde, superoxide dismutase, and serum total acid phosphatase increased by 97%, 25%, and 48%, respectively. Histology revealed poor architecture and severe proliferation of the prostate in BPH rats. Inflammation and oxidative stress markers, as well as the histological alteration in BPH rats, was attenuated (P < .05) upon cotreatment with PA and comparable with Fin cotreatment. These results suggest that PA mitigates oxido-inflammatory responses and restored prostatic cytoarchitecture to levels comparable with control in rats induced with BPH.

To determine the therapeutic effects of the Zhuangyao Jianshen pill (, ZYJSP) against benign prostatic hyperplasia (BPH) and investigate the underlying mechanism. Forty-eight male Sprague-Dawley rats were randomly divided into six groups: Control group, BPH model group, finasteride-treated group, ZYJSP low, medium and high dose groups. Except for the control group, 40 rats were castrated and injected with testosterone propionate (TP) for 28 consecutive day to induce BPH. Meanwhile, the corresponding drugs were administered by gavage. The prostate wet weight, prostate index (PI), and the histopathological changes in the prostate were measured as the basis for examining the efficacy of ZYJSP against BPH. Levels of the serum sex hormones, oxidative stress markers, inflammatory markers, renal function markers, growth factors, and Cyclin D1 expression in prostate were measured to characterize the therapeutic mechanism of ZYJSP against BPH. ZYJSP administration significantly reduced prostate wet weight and PI and ameliorated histological changes of the prostate in TP-treated castrated rats. TP markedly increased the levels of creatinine, blood urea nitrogen and growth factors in the serum as well as the expression of the Cyclin D1 in the prostate. Most of these markers were significantly decreased by ZYJSP. ZYJSP significantly restored the dysregulation of testosterone, estradiol, and dihydrotestosterone caused by TP. Furthermore, ZYJSP relieved TP-induced prostate injury and exhibited both anti-inflammatory and anti-oxidant activity by decreasing interleukin-6, interleukin-8, and malondialdehyde levels and increasing the activity of superoxide dismutase in the serum. These findings indicate that ZYJSP can effectively ameliorate BPH induced by TP in castrated rats, and the underlying mechanism might be related to regulating sex hormone balance, reducing oxidative stress, and inhibiting the inflammatory response.

Oxidative stress contributes to benign prostatic hyperplasia (BPH) pathogenesis, but its role in BPH with bladder diverticulum is unclear. This prospective cohort study compared 126 BPH patients at the Second Hospital of Harbin Medical University. The study involved two groups (n = 63 for each group): group A, comprising patients with BPH, and group B, consisting of BPH patients with bladder diverticulum. Ultrasound imaging and CT scans were employed to assess the features of BPH and bladder diverticulum, respectively. Various clinical parameters and oxidative stress biomarkers were compared between the groups. Group B exhibited significantly higher creatinine (101.8 ± 27.6 µmol/L vs. 56.1 ± 23.6 µmol/L, p < 0.0001), WBC counts (7.0 ± 1.9 vs. 4.2 ± 1.3 × 10⁹/L, p < 0.0001), residual urine volume (400.1 ± 252.0 mL vs. 150.7 ± 93.9 mL, p < 0.0001), and oxidative stress markers, including 8-OHdG (1.93 ± 0.58 vs. 1.70 ± 0.73 ng/mg creatinine, p = 0.014) and MDA (2.46 ± 0.57 vs. 2.03 ± 0.57 μmol/L, p < 0.0001). In group A, 8-OHdG positively correlated with residual urine volume (rho = 0.68) and nitric oxide with bladder wall thickness (rho = 0.70), while quality of life (QoL) negatively correlated with nitric oxide (rho = -0.76). In group B, oxidative stress markers correlated positively with BMI (e.g., homocysteine, rho = 0.69) and bladder wall thickness (e.g., nitric oxide, rho = 0.69), with QoL negatively correlated with uric acid (rho = -0.78). Bladder diverticulum in BPH patients is associated with elevated oxidative stress, increased inflammation, and impaired bladder function.

Chronic glaucoma is a multifactorial disease among which oxidative stress may play a major pathophysiological role. We conducted a systematic review and meta-analysis to evaluate the levels of oxidative and antioxidative stress markers in chronic glaucoma compared with a control group. The PubMed, Cochrane Library, Embase and Science Direct databases were searched for studies reporting oxidative and antioxidative stress markers in chronic glaucoma and in healthy controls using the following keywords: “oxidative stress” or “oxidant stress” or “nitrative stress” or “oxidative damage” or “nitrative damage” or “antioxidative stress” or “antioxidant stress” or “antinitrative stress” and “glaucoma”. We stratified our meta-analysis on the type of biomarkers, the type of glaucoma, and the origin of the sample (serum or aqueous humor). We included 22 case-control studies with a total of 2913 patients: 1614 with glaucoma and 1319 healthy controls. We included 12 studies in the meta-analysis on oxidative stress markers and 19 on antioxidative stress markers. We demonstrated an overall increase in oxidative stress markers in glaucoma (effect size = 1.64; 95%CI 1.20–2.09), ranging from an effect size of 1.29 in serum (95%CI 0.84–1.74) to 2.62 in aqueous humor (95%CI 1.60–3.65). Despite a decrease in antioxidative stress marker in serum (effect size = –0.41; 95%CI –0.72 to –0.11), some increased in aqueous humor (superoxide dismutase, effect size = 3.53; 95%CI 1.20–5.85 and glutathione peroxidase, effect size = 6.60; 95%CI 3.88–9.31). The differences in the serum levels of oxidative stress markers between glaucoma patients and controls were significantly higher in primary open angle glaucoma vs primary angle closed glaucoma (effect size = 12.7; 95%CI 8.78–16.6, P < 0.001), and higher in pseudo-exfoliative glaucoma vs primary angle closed glaucoma (effect size = 12.2; 95%CI 8.96–15.5, P < 0.001). In conclusion, oxidative stress increased in glaucoma, both in serum and aqueous humor. Malonyldialdehyde seemed the best biomarkers of oxidative stress in serum. The increase of some antioxidant markers could be a protective response of the eye against oxidative stress.

Metabolic syndrome (MetS) is a combination of metabolic disorders that can predispose individuals to benign prostatic hyperplasia (BPH). The inhibition of the cannabinoid 1 (CB1) receptor has been used to treat metabolic disorders in animal models. This study reports the use of a peripherally restricted CB1 antagonist (AM6545) and a neutral CB1 antagonist (AM4113) to improve MetS-related BPH in rats. Animals were divided into three control groups to receive either a normal rodent diet, AM6545, or AM4113. MetS was induced in the fourth, fifth, and sixth groups using a concentrated fructose solution and high-salt diet delivered as food pellets for eight weeks. The fifth and sixth groups were further given AM6545 or AM4113 for additional four weeks. Body and prostate weights were measured and prostate sections were stained with hematoxylin eosin. Cyclin D1, markers of oxidative stress and inflammation, and levels of the endocannabinoids were recorded. BPH in rats with MetS was confirmed through increased prostate weight and index, as well as histopathology.Treatment with either AM6545 or AM4113 significantly decreased prostate weight, improved prostate histology, and reduced cyclin D1 expression compared with the MetS group. Groups treated with CB1 antagonists experienced reduced lipid peroxidation, recovered glutathione depletion, restored catalase activity, and had lower inflammatory markers interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α). MetS rats treated with either AM6545 or AM4113 showed reduced concentrations of anandamide (AEA) and 2-arachidonoylglycerol (2-AG) in the prostate compared with the MetS group. In conclusion, the CB1 antagonists AM6545 and AM4113 protect against MetS-induced BPH through their anti-proliferative, antioxidant, and anti-inflammatory effects.

Modifiable Risk Factors for Benign Prostatic Hyperplasia and Lower Urinary Tract Symptoms: New Approaches to Old Problems

We assessed the effects of candesartan in addition to angiotensin-converting enzyme (ACE) inhibitors on N-terminal pro-type natriuretic peptide (Nt-proBNP), systemic markers of inflammation and oxidative stress as well as on glucose regulation in patients with heart failure (HF). Eighty patients with HF ages 62.5 +/- 8.4 years presenting mostly with New York Heart Association class II symptoms (class II = 57.5%, III = 41.3%), and mean left ventricular ejection fraction 27.1 +/- 7.3% were recruited. The patients were randomized to receive candesartan titrated to 32 mg 1 per day versus placebo in double-blind fashion for 6 months. Nt-proBNP, markers of inflammation and oxidative stress, glucose, insulin, and fasting insulin resistance index were analyzed. Candesartan decreased Nt-proBNP (median value = 12.4% versus -20.4%; [candesartan] P = .05), and high-sensitivity C-reactive protein (hsCRP) (+5.32% versus -20.3% [candesartan]; P = 0.046), without significantly influencing serum interleukin-6, interleukin-18, adhesion molecules, or markers of oxidative stress. Blood glucose decreased in patients treated with candesartan with a significantly greater effect in patients with higher blood glucose levels (P < .01 for interaction). The addition of candesartan to ACE inhibitor and beta-blocker decreases Nt-proBNP and hsCRP, but does not change the other markers of inflammation or oxidative stress in patients with heart failure. Dual angiotensin-II suppression also decreased blood glucose with a greater impact in patients with higher blood glucose level.

Identification of Differential Patterns of Oxidative Biomarkers in Prostate Cancer Progression.