Effects of the 5α-reductase Inhibitor Dutasteride on Rat Prostate α1A-adrenergic Receptor and Its Mediated Contractility

Wang, Dong; Zha, Xinmin; Nagase, Keiko; Akino, Hironobu; Muramatsu, Ikunobu; Ito, Hiroki; Yokoyama, Osamu

doi:10.1016/j.urology.2014.12.002

Cited by 7 publications

(5 citation statements)

References 25 publications

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“…These findings are contrary to those of Rhoden et al 21 who reported no changes in seminiferous tubules. But our findings are similar to the descriptions of Wang et al 25 and Cukierski et al 24 who reported finasteride-induced infertility with inhibited spermatogenesis.…”

Section: Discussionsupporting

confidence: 93%

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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: Discussionsupporting

confidence: 93%

“…In prior studies, DHT improved in the DA-9401 treated groups compared to the finasteride group. 2,25 Histological findings showed that the seminiferous tubule was disrupted significantly in the F group compared to the CTR group and was recovered by DA-9401 administration. Similar findings were found in TUNEL analysis.…”

Section: Discussionmentioning

confidence: 99%

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 prior studies, DHT improved in the DA-9401 treated groups compared to the finasteride group. 2 , 25 …”

Section: Discussionmentioning

confidence: 99%

Protective effect of DA-9401 in finasteride-induced apoptosis in rat testis: inositol requiring kinase 1 and c-Jun N-terminal kinase pathway

Soni¹,

Shin²,

Choi³

et al. 2017

DDDT

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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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“…At 4 months of age, animals were assigned to experimental groups. Wistar–Kyoto rats were randomly assigned to three groups: control Group (C, n = 10), which received distilled water; control plus dutasteride Group (C + D, n = 10), which received 0.5 mg kg −1 dutasteride 15 (Dastene 0.5 mg, Aché, Indaiatuba, SP, Brazil); and control plus finasteride Group (C + F, n = 10), which received 5 mg kg −1 finasteride 16 (Finasterida 5 mg, Eurofarma, São Paulo, SP, Brazil). SHRs were also randomly divided into three similar groups: BPH Group (H, n = 10), which received distilled water; BPH plus dutasteride Group (H + D, n = 10), which received dutasteride; and BPH plus finasteride Group (H + F, n = 10), which received finasteride.…”

Section: Methodsmentioning

confidence: 99%

The corpus cavernosum after treatment with dutasteride or finasteride: A histomorphometric study in a benign prostatic hyperplasia rodent model

Silva

et al. 2018

Asian J Androl

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Erectile dysfunction is a common side effect of finasteride and dutasteride treatments. The objective of this study was to investigate the structural changes in the penis using a benign prostatic hyperplasia (BPH) rodent model treated with dutasteride or finasteride. Sixty male rats were divided into the following groups: C, untreated control rats; C + D, control rats receiving dutasteride; C + F, control rats receiving finasteride; H, untreated spontaneously hypertensive rats (SHRs); H + D, SHRs treated with dutasteride; and H + F, SHRs treated with finasteride. Treatments were performed for 40 days, and penises were collected immediately thereafter. The organs were analyzed using histomorphometric methods to determine the cross-sectional penile area, as well as the surface density (Sv) of smooth muscle fibers, connective tissue, elastic system fibers, and sinusoidal spaces of the corpus cavernosum. The results were compared using a one-way ANOVA with Bonferroni's posttest. Groups C + D and C + F had a significantly smaller penile cross-sectional area, but more elastic system fiber Sv compared to Group C. Group C + D showed less smooth muscle Sv, and Group H showed more connective tissue but a smaller sinusoidal space Sv in the corpus cavernosum compared to Group C. Groups H + D and H + F had less smooth muscle Sv than Group H. Group H + D also had more connective tissue and elastic system fiber Sv than Group H. Both dutasteride and finasteride promoted penile modifications in the control rat penis, although this affect was greater in Group H animals. In this rodent model, dutasteride was the drug that most affected the corpus cavernosum.

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Effects of the 5α-reductase Inhibitor Dutasteride on Rat Prostate α1A-adrenergic Receptor and Its Mediated Contractility

Cited by 7 publications

References 25 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

Protective effect of DA-9401 in finasteride-induced apoptosis in rat testis: inositol requiring kinase 1 and c-Jun N-terminal kinase pathway

The corpus cavernosum after treatment with dutasteride or finasteride: A histomorphometric study in a benign prostatic hyperplasia rodent model

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