scholarly journals Periodontitis Exacerbates Benign Prostatic Hyperplasia through Regulation of Oxidative Stress and Inflammation

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Cheng Fang ◽  
Lan Wu ◽  
Ming-Juan Zhao ◽  
Tong Deng ◽  
Jia-Min Gu ◽  
...  

Epidemiological studies demonstrate that men with periodontitis are also susceptible to benign prostatic hyperplasia (BPH) and that periodontal treatment can improve the prostatic symptom. However, molecular links of this relationship are largely unknown. The goal of the current study was to elucidate the effects of experimental periodontitis on the hyperplasia of prostate and whether oxidative stress and inflammation participated in this process. For this purpose, ligature-induced periodontitis, testosterone-induced BPH, and the composite models in rats were established. Four weeks later, all the rats were sacrificed and the following items were measured: alveolar bone loss and histological examination of periodontal tissues were taken to assess the establishment of periodontitis model, prostate index and histological examination of prostate tissues were taken to test the establishment of the BPH model, inflammatory cytokines in plasma were assessed, and Bax/Bcl-2 proteins related to cell apoptosis were analyzed via western blot analysis. To further investigate whether oxidative stress participates in the aggravation of BPH, in vitro models were also conducted to measure the production of intracellular reactive oxygen species (ROS) and hydrogen peroxide (H2O2) concentration. We found that simultaneous periodontitis and BPH synergistically aggravated prostate histological changes, significantly increased Ki67 proliferation, and reduced apoptosis in rat prostate tissues. Also, our results showed that periodontal ligation induced increased Bcl-2 protein expression, whereas Bax expression was decreased in BPH rats than in normal rats. Compared with the control group, periodontitis and BPH both significantly enhanced inflammatory cytokine levels of TNF-α, IL-6, IL-1β, and CRP. Furthermore, Porphyromonas gingivalis lipopolysaccharide induced enhanced generation of intracellular expression of ROS and H2O2 in BPH-1 cells. Our experimental evidence demonstrated that periodontitis might promote BPH development through regulation of oxidative stress and inflammatory process, thus providing new strategies for prevention and treatment of BPH.

Molecules ◽  
2018 ◽  
Vol 23 (10) ◽  
pp. 2638 ◽  
Author(s):  
Bo-Ram Jin ◽  
Hyo-Jung Kim ◽  
Sang-Kyun Park ◽  
Myoung-Seok Kim ◽  
Kwang-Ho Lee ◽  
...  

Benign prostatic hyperplasia (BPH), an age-dependent disorder with a prevalence percentage of 60% in the 60s, has been found to involve an androgenic hormone imbalance that causes confusion between cell apoptosis and proliferation. Because general medications for BPH treatment have undesirable side effects, the development of effective alternative medicines has been considered. HBX-5 is a newly developed formula with the aim of improving BPH, and is composed of nine medicinal herbs. BPH was induced in the rats by intramuscular injection of testosterone propionate after castration. Rats were divided into six groups, and the efficacy of HBX-5 on testosterone-induced BPH in rats was estimated. In addition, RWPE-1 and WPMY-1 cells were used to demonstrate the effect of HBX-5 on BPH in vitro model. Compared with the control group, HBX-5 administration group suppressed BPH manifestations, such as excessive development of prostate, and increase of serum dihydrotestosterone and 5α-reductase concentrations. Furthermore, immunohistochemistry analysis revealed that HBX-5 significantly decreased the expression of androgen receptor (AR) and proliferating cell nuclear antigen (PCNA). In addition, results of RWPE-1 and WPMY-1 cells showed that HBX-5 inhibited the over-expression of AR and PSA in DHT-induced prostate hyperplastic microenvironments.


2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Yanbo Chen ◽  
Hui Xu ◽  
Chong Liu ◽  
Meng Gu ◽  
Qi Chen ◽  
...  

The pathogenesis of benign prostatic hyperplasia (BPH) is extremely complicated which involving the multiple signaling pathways. The deficiency of vitamin D is an important risk factor for BPH, and exogenous vitamin D is effective for the treatment of BPH. In this study, we provided in vitro mechanical evidence of vitamin D as a treatment for BPH using BPH-1, WPMY-1, and PBMC cells. We found that 25-hydroxyvitamin D (25-OH D) level is decreased in BPH and closely correlated with age, prostate volume, maximum flow, international prostate symptom score, and prostate-specific antigen of the BPH patients. We further revealed that 25-OH D ameliorated TGF-β1 induces epithelial-mesenchymal transition (EMT) of BPH-1 cells and proliferation of WPMY-1 cells via blocking TGF-β signaling. Moreover, 25-OH D was able to block NF-κB signaling in PBMCs of BPH patients and STAT3 signaling in BPH cells to relieve inflammation. 25-OH D also protects BPH cells from inflammatory cytokines selected by PBMCs. Finally, we uncovered that 25-OH D alleviated prostate cell oxidative stress by triggering Nrf2 signaling. In conclusion, our data verified that 25-OH D regulated multiple singling pathways to restrain prostate cell EMT, proliferation, inflammation, and oxidative stress. Our study provides in vitro mechanical evidence to support clinical use of vitamin D as a treatment for BPH.


2019 ◽  
Author(s):  
Shanika Karunasagara ◽  
Geum-Lan Hong ◽  
Da-Young Jung ◽  
Kyung-Hyun Kim ◽  
Eun-Jeong Koh ◽  
...  

AbstractBenign prostatic hyperplasia (BPH) is a progressive pathological condition associated with proliferation of prostatic tissues, prostate enlargement, and lower-urinary tract symptoms. However, the mechanism underlying the pathogenesis of BPH is not clear. The aim of this study was to investigate the protective effects of Stauntonia hexaphylla and Cornus officinalis (SC extract) on a testosterone propionate (TP)-induced BPH model. For in vitro experiments, a human prostate adenocarcinoma cell line was used to perform western blotting for androgen receptor (AR), prostate specific antigen (PSA), and 5α-reductase type 2. Male Sprague-Dawley rats were randomly divided into 8 groups as follows for the in vivo experiments: control, BPH, Fina, Saw, SC25, SC50, SC100, and SC200. To induce BPH, all rats, except those in the control group, were daily administered with subcutaneous injections of TP (5 mg/kg), and orally treated with appropriate PBS/drugs for 4 consecutive weeks. Our findings indicated that the SC treatment significantly reduced the prostate size and downregulated the serum testosterone and DHT levels in BPH rats. The histological examination revealed that SC treatment markedly recovered the TP-induced abnormalities and reduced the prostatic hyperplasia. In addition, in vitro and in vivo western blotting indicated that SC treatment significantly downregulated the AR, PSA, and 5α-reductase type 2 expression, while an immunohistochemistry examination revealed that the SC extract significantly reduced the expression of type 2 5α-reductase and proliferating cell nuclear antigen positive cell count. Collectively, our findings demonstrated that SC extract attenuates BPH through anti-proliferative and anti-inflammation activities and might be useful in the clinical treatment of BPH.


Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 2203 ◽  
Author(s):  
Jin ◽  
Kim ◽  
Kim ◽  
Chung ◽  
Ha ◽  
...  

Abstract: Background: 6′-Sialyllactose (6SL) displays a wide range of the bioactive benefits, such as anti-proliferative and anti-angiogenic activities. However, the therapeutic effects of 6SL on benign prostatic hyperplasia (BPH) remain unknown. Methods: Six-week-old male Wistar rats (n = 40) were used for in vivo experiments. All rats were castrated and experimental BPH was induced in castrated rats by intramuscular injection of testosterone, with the exception of those in the control group. Rats with BPH were administrated finasteride and 0.5 or 1.0 mg/kg 6SL. Furthermore, the inhibitory effects of 6SL on human epithelial BPH cell line (BPH-1) cells were determined in vitro. Results: Rats with BPH exhibited outstanding BPH manifestations, including prostate enlargement, histological alterations, and increased prostate-specific antigen (PSA) levels. Compared to those in the BPH group, rats in the 6SL group showed fewer pathological changes and normal androgen events, followed by restoration of retinoblastoma protein (pRb) and cell cycle-related proteins. In BPH-1 cells, treatment with 6SL significantly suppressed the effects on the androgen receptor (AR), PSA, and E2F transcription factor 1 (E2F1)-dependent cell cycle protein expression. Conclusions: 6SL demonstrated anti-proliferative effects in a testosterone-induced BPH rat model and on BPH-1 cells by regulating the pRB/E2F1–AR pathway. According to our results, we suggest that 6SL may be considered a potential agent for the treatment of BPH.


Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 450
Author(s):  
Kensuke Mitsunari ◽  
Yasuyoshi Miyata ◽  
Tomohiro Matsuo ◽  
Yuta Mukae ◽  
Asato Otsubo ◽  
...  

Benign prostatic hyperplasia (BPH) is arguably the most common benign disease among men. This disease is often associated with lower urinary tract symptoms (LUTS) in men and significantly decreases the quality of life. Polyphenol consumption reportedly plays an important role in the prevention of many diseases, including BPH. In recent years, in addition to disease prevention, many studies have reported the efficacy and safety of polyphenol treatment against various pathological conditions in vivo and in vitro. Furthermore, numerous studies have also revealed the molecular mechanisms of the antioxidant and anti-inflammatory effects of polyphenols. We believe that an improved understanding of the detailed pharmacological roles of polyphenol-induced activities at a molecular level is important for the prevention and treatment of BPH. Polyphenols are composed of many members, and their biological roles differ. In this review, we first provide information regarding the pathological roles of oxidative stress and inflammation in BPH. Next, the antioxidant and anti-inflammatory effects of polyphenols, including those of flavonoids and non-flavonoids, are discussed. Finally, we talk about the results and limitations of previous clinical trials that have used polyphenols in BPH, with particular focus on their molecular mechanisms of action.


2016 ◽  
Vol 41 (12) ◽  
pp. 1303-1310 ◽  
Author(s):  
Guan-Yu Ren ◽  
Chun-Yang Chen ◽  
Wei-Guo Chen ◽  
Ya Huang ◽  
Li-Qiang Qin ◽  
...  

Secoisolariciresinol diglucoside (SDG), a lignan extracted from flaxseed, has been shown to suppress benign prostatic hyperplasia (BPH). However, little is known about the mechanistic basis for its anti-BPH activity. The present study showed that enterolactone (ENL), the mammalian metabolite of SDG, shared the similar binding site of G1 on a new type of membranous estrogen receptor, G-protein-coupled estrogen eceptor 1 (GPER), by docking simulations method. ENL and G1 (the specific agonist of GPER) inhibited the proliferation of human prostate stromal cell line WPMY-1 as shown by MTT assay and arrested cell cycle at the G0/G1 phase, which was displayed by propidium iodide staining following flow cytometer examination. Silencing GPER by short interfering RNA attenuated the inhibitory effect of ENL on WPMY-1 cells. The therapeutic potential of SDG in the treatment of BPH was confirmed in a testosterone propionate-induced BPH rat model. SDG significantly reduced the enlargement of the rat prostate and the number of papillary projections of prostatic alveolus and thickness of the pseudostratified epithelial and stromal cells when comparing with the model group. Mechanistic studies showed that SDG and ENL increased the expression of GPER both in vitro and in vivo. Furthermore, ENL-induced cell cycle arrest may be mediated by the activation of GPER/ERK pathway and subsequent upregulation of p53 and p21 and downregulation of cyclin D1. This work, in tandem with previous studies, will enhance our knowledge regarding the mechanism(s) of dietary phytochemicals on BPH prevention and ultimately expand the scope of adopting alternative approaches in BPH treatment.


2009 ◽  
Vol 88 (8) ◽  
pp. 752-756 ◽  
Author(s):  
A. Miyagawa ◽  
M. Chiba ◽  
H. Hayashi ◽  
K. Igarashi

During orthodontic tooth movement, the activation of the vascular system in the compressed periodontal ligament (PDL) is an indispensable process in tissue remodeling. We hypothesized that compressive force would induce angiogenesis of PDL through the production of vascular endothelial growth factor (VEGF). We examined the localization of VEGF in rat periodontal tissues during experimental tooth movement in vivo, and the effects of continuous compressive force on VEGF production and angiogenic activity in human PDL cells in vitro. PDL cells adjacent to hyalinized tissue and alveolar bone on the compressive side showed marked VEGF immunoreactivity. VEGF mRNA expression and production in PDL cells increased, and conditioned medium stimulated tube formation. These results indicate that continuous compressive force enhances VEGF production and angiogenic activity in PDL cells, which may contribute to periodontal remodeling, including angiogenesis, during orthodontic tooth movement.


2021 ◽  
pp. 5-9
Author(s):  
Prasenjit Bhowmik ◽  
Soumendranath Mandal ◽  
Gaurav Sharma ◽  
Bandhan Bahal ◽  
Prashant Gupta ◽  
...  

Objectives: To dene the diagnostic accuracy of intravesical protrusion of prostate (IPP), bladder wall thickness (BWT) and prostate volume (PV) in diagnosis of bladder outlet obstruction (BOO) and prediction of future acute urinary retention (AUR). A prospective Materials and methods: study of 127 patients, presenting with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (BPH) were enrolled with 50 patients among them manifesting AUR. 35 normal persons were selected as control group. After inclusion, all patients underwent transabdominal ultrasound and pressure ow urodynamic study (UDS). UDS parameter, BOO index (BOOI) were used as a reference standard for stratifying the patients into two groups, BOO and non-BOO. The sono-morphological parameters, IPP, BWT and PV were used to compare between these two groups with calculating the diagnostic accuracy for each individual index. IPP, BWT Results: and PV had statistically signicant difference between group 1 (BOOI < 40) and 2 ( BOOI > 40) with strong correlation with BOOI. The Pearson's correlation coefcient (r) for IPP, BWT and PV were 0.762, 0.702 and 0.660 respectively. The AUC for IPP, BWT and PV were 0.824, 0.786 and 0.650 with highest accuracy for IPP (79.2%) at cutoff value of 7 mm. Using the same threshold value, IPP had higher statistical difference than BWT in predicting AUR with similar diagnostic accuracy of IPP and BWT together. IPP and BWT in conjunction with PV in place Conclusions: of UDS had good clinical utility in diagnosis of BOO due to BPH and future AUR prediction.


2020 ◽  
Vol 5 (2) ◽  
pp. 104
Author(s):  
Destri Khusnul Khotimah ◽  
I Wayan Arya Krishnawan Firdaus ◽  
Maharani Laillyza Apriasari

ABSTRACTBackground: Chronic periodontitis is an infectious disease that causes damage on periodontal ligament and alveolar bone. The severity of periodontitis is caused by several types of bacterial species which one of them is Porphyromonas gingivalis bacteria with a prevalence of 85% in oral cavity. The extract of kelakai leaf contained antibacterial in the form of flavonoid, alkaloid, tannin, and steroid. Flavonoid consists of some chemical compounds which is one of them is quercetin. The level of quercetin in kelakai leaf is 503.56 mgQE/g. From some secondary metabolites, kelakai leaf has inhibitory power toward gram negative bacterial, Porphyromonas gingivalis. Objective: This research was intended to know the activity of inhibitory power of kelakai leaf toward Porphyromonas gingivalis bacteria. Method: This research was an experimental research consisted of 5 experimental groups that were group of kelakai leaf extract on the concentrations of 100 mh/ml, 75 mg/ml, 50mg/ml, and 25 mg/ml and the control group (0.2% chlorhexidine). Each treatment was done in 4 repetitions. The test of inhibitory power used diffusion method by measuring the inhibitory zone around the growth of Porphyromonas gingivalis on Mueller Hinton Agar media. The data were analyzed by using One Way Anova 95% and then continued with LSD. Results: Based on the LSD test, it was known that the extract of Kelakai leaf had inhibitor power activity toward Porphyromonas gingivalis. The highest inhibitory zone was on the concentration of 100 mg/ml with inhibitory zone of 14.61 mm. Conclusion: The extract of kelakai leaf had inhibitory power activity toward Porphyromonas gingivalis bacteria in vitro. Keywords: 0.2% chlorhexidine, Diffusion method, Inhibitory power, Stenochlaena palustris extract, Porphyromonas gingivalis.


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