Histologic Evaluation of Human Benign Prostatic Hyperplasia Treated by Dutasteride: A Study by Xenograft Model With Improved Severe Combined Immunodeficient Mice

Tsujimura, Akira; Fukuhara, Shinichiro; Soda, Tetsuji; Takezawa, Kentaro; Kiuchi, Hiroshi; Takao, Tetsuya; Miyagawa, Yasushi; Nonomura, Norio; Adachi, Souichi; Tokita, Yoriko; Nomura, Taisei

doi:10.1016/j.urology.2014.09.024

Cited by 13 publications

(8 citation statements)

References 28 publications

(32 reference statements)

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“…Regarding the relationship between finasteride and reproductive organs, evidences linking finasteride with apoptosis in prostate cells have been published. 34 In contrast to these results, we found apoptosis markers procaspase-3 and its active form cleaved caspase-3 in the F group, showing that finasteride may cause apoptosis in testicular tissue.…”

Section: Discussioncontrasting

confidence: 95%

446 Protective Effect of DA-9401 in Finasteride-Induced Apoptosis in Rat Testis: Inositol Requiring Kinase 1 and C-Jun N-Terminal Kinase Pathway

Soni

Shin

Choi

et al. 2018

The Journal of Sexual Medicine

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Finasteride is used to treat male pattern baldness and benign prostatic hyperplasia. This study investigated the toxicity of finasteride and recovery by DA-9401 using Sprague Dawley (SD) rats. Forty adult male SD rats were assigned to four groups: control (CTR), finasteride 1 mg/kg/day (F), finasteride 1 mg/kg + DA-9401 100 mg/kg/day (F + DA 100) and finasteride 1 mg/kg + DA-9401 200 mg/kg/day (F + DA 200). Treatments were by oral delivery once daily for 90 consecutive days. The gross anatomical parameters assessed included: genital organ weight; vas deferens sperm count and sperm motility; testosterone, dihydrotestosterone (DHT) and malondialdehyde levels; and histological and terminal deoxynucleotidyl transferase enzyme mediated dUTP nick-end labeling (TUNEL) staining of testis for spermatogenic cell density, Johnsen's score and apoptosis. Testicular tissue was also used for evaluating endoplasmic reticulum (ER) stress and apoptotic proteins. Epididymis weight, seminal vesicle weight, prostate weight, penile weight and vas deferens sperm motility showed significant differences between the F group and the CTR, F + DA 100 and F + DA 200 groups. There was no significant change in the testosterone level. DHT level decreased significantly in the F group compared with the CTR group. Testis tissue revealed significant changes in spermatogenic cell density, Johnsen's score and apoptotic index. Western blot showed significant changes in the ER stress and apoptotic markers. Finasteride resulted in reduced fertility and increased ER stress and apoptotic markers, which were recovered by administration of DA-9401 in the SD rats.

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Section: Discussioncontrasting

confidence: 95%

446 Protective Effect of DA-9401 in Finasteride-Induced Apoptosis in Rat Testis: Inositol Requiring Kinase 1 and C-Jun N-Terminal Kinase Pathway

Soni

Shin

Choi

et al. 2018

The Journal of Sexual Medicine

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“…In a rat model of chronic bacterial prostatitis, finasteride statistically significantly decreased bacterial growth and reduced inflammatory cell infiltrations [ 34 ]. In a mouse xenograft model of human BPH, dutasteride reduced staining of cyclooxygenase-2 (Cox-2) and Ras homolog gene family, member A (RhoA) after already 2 months [ 5 , 35 ]. In contrast, another study in a mouse model of BPH showed that finasteride increased persistent PIS (i.e., CD45 + cell foci) [ 36 ].…”

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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“…In addition, patients with prostatitis‐like symptoms including irritative bladder symptoms had improved symptoms following dutasteride treatment compared to those given placebo 7 . Finally, dutasteride treatment in a mouse BPH xenograft model reduced expression of the proinflammatory mediator COX‐2 in prostate tissue 8 . These results suggest that dutasteride could have an anti‐inflammatory effect in the prostate although underlying mechanisms are unclear.…”

Section: Introductionmentioning

confidence: 90%

“…7 Finally, dutasteride treatment in a mouse BPH xenograft model reduced expression of the proinflammatory mediator COX-2 in prostate tissue. 8 These results suggest that dutasteride could have an anti-inflammatory effect in the prostate although underlying mechanisms are unclear.…”

Section: Introductionmentioning

confidence: 97%

Effects of dutasteride in a rat model of chemically induced prostatic inflammation—Potential role of estrogen receptor β

et al. 2020

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Background: Dutasteride administration reportedly improves lower urinary tract symptoms in patient with chronic, histologically-identified prostatic inflammation, potentially through estrogen receptor β (ERβ), activation of which has antiinflammatory effects in the prostate tissue. Therefore, we investigated the effect of dutasteride on intraprostatic inflammatory responses and bladder activity using a rat model of chemically induced prostatic inflammation. Methods: Male Sprague-Dawley rats at 10 weeks old were used. Prostatic inflammation was induced by 5% formalin injection into ventral lobes of the prostate and saline was injected in the control group (control, n = 5). Rats with prostatic inflammation were divided into dutasteride therapy (dutasteride, n = 5) and placebo groups (placebo, n = 5). Dutasteride was administrated at a dose of 0.5 mg/kg daily from 2 days before induction of prostatic inflammation whereas placebo rats received vehicle only. Twenty-eight days later, cystometry was performed in a conscious condition to measure non-voiding contractions (NVCs), intercontraction intervals (ICI) and postvoid residual volume (RV). After cystometry, the prostate was excised for analysis of messenger RNA (mRNA) expression levels of ERα, ERβ, interleukin-1β (IL-1β), and IL-18 by quantitative polymerase chain reaction. Results: The mean number of NVCs was significantly greater in placebo group than that of control group without prostatic inflammation (p < .05), and ICI were significantly decreased in placebo group compared with control group (p < .05). On the contrary, there was no significant change in NVCs or ICI between control and dutasteride groups. RV was not significantly different among three groups. Gene expression levels of ERα, IL-1β, and IL-18 was significantly increased in placebo rats compared with control rats (p < .05), but not significantly different between control and dutasteride rats. On the other hand, the mRNA expression level of ERβ was significantly decreased in placebo rats (p < .05), but not in dutasteride rats, compared with control rats. Conclusion: Dutasteride treatment improved not only prostatic inflammation evident as increased gene expression levels in IL-1β and IL-18, but also bladder overactivity shown by increased NVCs during bladder filling. These therapeutic effects were associated with the restored expression of anti-inflammatory ERβ. Therefore, dutasteride might be

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Histologic Evaluation of Human Benign Prostatic Hyperplasia Treated by Dutasteride: A Study by Xenograft Model With Improved Severe Combined Immunodeficient Mice

Cited by 13 publications

References 28 publications

446 Protective Effect of DA-9401 in Finasteride-Induced Apoptosis in Rat Testis: Inositol Requiring Kinase 1 and C-Jun N-Terminal Kinase Pathway

446 Protective Effect of DA-9401 in Finasteride-Induced Apoptosis in Rat Testis: Inositol Requiring Kinase 1 and C-Jun N-Terminal Kinase Pathway

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

Effects of dutasteride in a rat model of chemically induced prostatic inflammation—Potential role of estrogen receptor β

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