Histologic Influence of Doxazosin and Finasteride in Benign Prostatic Hyperplasia Accompanying Chronic Inflammation

Park, Dong Soo; Shim, Jae‐Yong

doi:10.1159/000167844

Cited by 9 publications

(5 citation statements)

References 32 publications

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“…Just like that hypoxia and angiogenesis are common findings in human BPH tissue [33,34], our EAP model successfully simulated BPH-related pathological conditions such as chronic inflammatory cell infiltration, hypoxia, and angiogenesis. On the other hand, it has been reported that reduced apoptosis often occurs in inflamed atrophic lesions [35,36], which may involve the potential carcinogenic effects of chronic or recurrent inflammation [18]. Although there is no evidence that human BPH will progress to prostate cancer, a reduction in apoptosis in the EAP rat prostates of this study was observed, and KLK1 administration restored the level of apoptosis of them.…”

Section: Discussioncontrasting

confidence: 53%

Tissue Kallikrein Protects Rat Prostate against the Inflammatory Damage in a Chronic Autoimmune Prostatitis Model via Restoring Endothelial Function in a Bradykinin Receptor B2-Dependent Way

Zhang

Lin

Luo

et al. 2022

Oxidative Medicine and Cellular Longevity

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Objective. The aim of this study was to investigate whether tissue kallikrein (KLK1) can protect the prostate from inflammatory damage and the mechanism involved in it. Methods. A total of 50 male Wistar rats were used in this study. Initially, 20 rats were sacrificed to obtain the prostate antigen to induce experimental autoimmune prostatitis (EAP), and the remaining 30 rats were randomly divided into 5 experimental groups (normal control group (NC group), NC+KLK1 group (NCK group), EAP group, EAP+KLK1 group (EAPK group), and EAP+KLK1+HOE140 group (EAPKH group); n = 6 ). It should be explained that KLK1 mainly exerts its biological effects through bradykinin, and HOE140 is a potent and selective bradykinin receptor B2 (BDKRB2) antagonist. EAP was induced by intradermal injection of 15 mg/ml prostate antigen and complete Freund’s adjuvant on days 0, 14, and 28. KLK1 was injected via tail vein at a dose of 1.5 × 10 − 3 PAN U/kg once a day, and HOE140 was administered by intraperitoneal injection at 20 μg/kg once every two days. Rats were sacrificed on day 42. The RNA and protein of the rat prostate were extracted to analyze the expression differences of KLK1, as well as the inflammation-, fibrosis-, and oxidative stress-related genes. The inflammatory cell infiltration and microvessel density of the prostate were also analyzed by pathological examination. In addition, pathological analysis was performed on prostate samples from patients undergoing benign prostate hyperplasia (BPH) surgery. Results. The expression of KLK1 in the prostate decreased in the EAP group as well as BPH patients with obvious inflammation. KLK1 administration significantly inhibited inflammatory cell infiltration and reduced the production of inflammatory cytokines in the EAPK group. Prostate samples from the EAP group showed increased infiltration of T cells and macrophages, as well as gland atrophy, hypoxia, fibrosis, and angiogenesis. KLK1 administration upregulated endothelial nitric oxide synthase (eNOS) expression and suppressed oxidative stress, as well as transforming growth factor β1 (TGF-β) signaling pathways and the proangiogenic vascular endothelial growth factor (VEGF) in the EAPK group. However, in the EAPKH group in which HOE140 blocked BDKRB2, the beneficial effects of KLK1 were all cancelled. In addition, KLK1 intervention in normal rats had no obvious side effects. Conclusion. The KLK1 expression is inhibited in the inflamed prostates of humans and rats. Exogenous KLK1 restored endothelial function via a BDKRB2-dependent way and then played a role in improving microcirculation and exerted anti-inflammatory, antifibrotic, and antioxidative stress effects in the rat chronic-inflamed prostate.

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Section: Discussioncontrasting

confidence: 53%

Tissue Kallikrein Protects Rat Prostate against the Inflammatory Damage in a Chronic Autoimmune Prostatitis Model via Restoring Endothelial Function in a Bradykinin Receptor B2-Dependent Way

Zhang

Lin

Luo

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…Vignozzi et al highlighted that DHT exerts an immune regulatory role on human prostatic stromal cells, inhibiting their potential to actively induce and/or sustain autoimmune and inflammatory responses [27]. Park and Shim found that finasteride might interfere with the anti-inflammatory reaction induced by doxazosin in combination of doxazosin and finasteride treatment [28]. Here we detected more patients and identified the T cell subsets which infiltrated in the prostatic tissue after finasteride treatment.…”

Section: Discussionmentioning

confidence: 69%

Low Intraprostatic DHT Promotes the Infiltration of CD8+ T Cells in BPH TissuesviaModulation of CCL5 Secretion

Fan

Zhou

Liu

et al. 2014

Mediators of Inflammation

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Clinical studies suggested thatandrogen might be associated with infiltrating T cells in prostate of benign prostatic hyperplasia (BPH) patients, but detail of T-cell subset and mechanism still remained unclear. The present study tested the hypothesis that intraprostatic 5α-dihydrotestosterone (DHT) exerts effects on T cells recruitment by BPH epithelial cells. Prostate tissues from 64 cases of BPH patients after transurethral resection of prostate (TURP) were divided into 2 groups: (1) no medication history; (2) administration of 5α-reductase type II inhibitor-finasteride 5 mg daily for at least 6 months before surgery. Group 2 presented significantly higher CD8+ T cells infiltration than group 1, but no changes in CD4+ T cells (immunohistochemistry and flow cytometry). In vitro study more CD8+ T cell migrated to the prostate tissue lysates from group 2 and BPH-1 cells in low DHT condition. Transcription of chemokine (C-C motif) Ligand 5 (CCL5) mRNA in BPH-1 cells and chemokine (C-C motif) receptor 5 (CCR5) mRNA in CD8+ T cells were upregulated in low DHT condition (q-PCR). CCL5 expression was also identified to be higher in group 2 prostate tissues by IHC. This study suggested that intraprostatic DHT may participate in regulating inflammatory response which was induced by human prostatic epithelial cell, via modulating CCL5 secretion.

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“…In contrast, another study in a mouse model of BPH showed that finasteride increased persistent PIS (i.e., CD45 + cell foci) [ 36 ]. In a study of 17 patients with BPH undergoing transurethral resection of the prostate (TURP), doxazosin ( N = 4) reduced the staining of CD3 and CD68 compared to no treatment ( N = 5) [ 37 ]. Glutathion-S-transferase pi-1 (GSTP1: inactivates oxidant carcinogens) expression was only decreased in patients receiving both doxazosin and finasteride ( N = 8) suggesting that finasteride may interfere with the anti-inflammatory effect of doxazosin.…”

Section: Methodsmentioning

confidence: 99%

Inflammation is a target of medical treatment for lower urinary tract symptoms associated with benign prostatic hyperplasia

et al. 2020

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Purpose To review the role of a persistent prostatic inflammatory status (PIS) in the development and progression of benign prostatic hyperplasia (BPH) associated with lower urinary tract symptoms (LUTS) and which medical therapies approved for LUTS/BPH may reduce persistent PIS. Methods Literature search in PubMed up to July 2019. Results The cause of histologically defined persistent PIS or chronic prostatic inflammation is multifactorial. It is evident in many men with LUTS/BPH, particularly in older men and in men with a large prostate volume or more severe (storage) LUTS. Additionally, persistent PIS is associated with an increased risk of acute urinary retention and symptom worsening. Of medical therapies approved for LUTS/BPH, the current evidence for a reduction of persistent PIS is greatest for the hexanic extract of Serenoa repens (HESr). This treatment relieves LUTS to the same extent as α1-adrenoceptor antagonists and short-term 5α-reductase inhibitors. Limited evidence is available on the effect of other mainstream LUTS/BPH treatments on persistent PIS. Conclusions Persistent PIS plays a central role in both the development and progression of LUTS/BPH. In men with LUTS/BPH who have a high chance of harbouring persistent PIS, HESr will not only improve LUTS, but also reduce (underlying) inflammation. Well-designed clinical studies, with a good level of evidence, are required to better evaluate the impact of BPH/LUTS medical therapies on persistent PIS.

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Histologic Influence of Doxazosin and Finasteride in Benign Prostatic Hyperplasia Accompanying Chronic Inflammation

Cited by 9 publications

References 32 publications

Tissue Kallikrein Protects Rat Prostate against the Inflammatory Damage in a Chronic Autoimmune Prostatitis Model via Restoring Endothelial Function in a Bradykinin Receptor B2-Dependent Way

Tissue Kallikrein Protects Rat Prostate against the Inflammatory Damage in a Chronic Autoimmune Prostatitis Model via Restoring Endothelial Function in a Bradykinin Receptor B2-Dependent Way

Low Intraprostatic DHT Promotes the Infiltration of CD8+ T Cells in BPH TissuesviaModulation of CCL5 Secretion

Inflammation is a target of medical treatment for lower urinary tract symptoms associated with benign prostatic hyperplasia

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