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Title: The therapeutic effects of docosahexaenoic acid on oestrogen/androgen-induced benign prostatic hyperplasia in rats

Abstract

Benign prostatic hyperplasia (BPH) is one of the major disorders of the urinary system in elderly men. Docosahexaenoic acid (DHA) is the main component of n-3 polyunsaturated fatty acids (n-3 PUFAs) and has nerve protective, anti-inflammatory and tumour-growth inhibitory effects. Here, the therapeutic potential of DHA in treating BPH was investigated. Seal oil effectively prevented the development of prostatic hyperplasia induced by oestradiol/testosterone in a rat model by suppressing the increase of the prostatic index (PI), reducing the thickness of the peri-glandular smooth muscle layer, inhibiting the proliferation of both prostate epithelial and stromal cells, and downregulating the expression of androgen receptor (AR) and oestrogen receptor α (ERα). An in vitro study showed that DHA inhibited the growth of the human prostate stromal cell line WPMY-1 and the epithelial cell line RWPE-1 in a dose- and time-dependent manner. In both cell lines, the DHA arrested the cell cycle in the G2/M phase. In addition, DHA also reduced the expression of ERα and AR in the WPMY-1 and RWPE-1 cells. These results indicate that DHA inhibits the multiplication of prostate stromal and epithelial cells through a mechanism that may involve cell cycle arrest and the downregulation of ERα and AR expression.more » - Highlights: • Seal oil prevents oestradiol/testosterone (E2/T)-induced BPH in castrated rats. • Seal oil downregulates the expression of oestrogen receptor α(ERα) and androgen receptor (AR) in rat BPH tissues. • DHA inhibits the growth of human prostate stromal and epithelial cells in vitro. • DHA arrests human prostate stromal and epithelial cells in the G2/M phase and downregulates the expression of cyclin B1. • DHA inhibits the expression of ERα and AR in human prostate stromal and epithelial cells.« less

Authors:
 [1];  [2]; ; ; ;  [1];  [2];  [3];  [4];  [1]
  1. Department of Biochemistry and Molecular Biology, College of Life Sciences, Bioactive Materials Key Lab of Ministry of Education, Nankai University, Tianjin 300071 (China)
  2. Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin 300211 (China)
  3. Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193 (China)
  4. Department of Histology and Embryology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070 (China)
Publication Date:
OSTI Identifier:
22648592
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 345; Journal Issue: 2; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ACTIN; ANIMAL TISSUES; ANTIGENS; BPH; CARBOXYLIC ACIDS; CELL CYCLE; DOSES; ESTROGENS; GTP-ASES; HUMAN POPULATIONS; HYPOXANTHINE; HYPOXANTHINE PHOSPHORIBOSYLTRANSFERASE; IN VITRO; INDEXES; INFLAMMATION; LAYERS; MEN; MUSCLES; NEOPLASMS; NERVES; OILS; OXIDOREDUCTASES; PHOSPHATES; PLANT GROWTH; PLANT TISSUES; POTENTIALS; PROLIFERATION; PROSTATE; RATS; RECEPTORS; SEALS; TESTOSTERONE; THICKNESS; TIME DEPENDENCE

Citation Formats

Wang, Chao, Luo, Fei, Zhou, Ying, Du, Xiaoling, Shi, Jiandang, Zhao, Xiaoling, Xu, Yong, Zhu, Yan, Hong, Wei, E-mail: hongwei@tijmu.edu.cn, and Zhang, Ju, E-mail: zhangju@nankai.edu.cn. The therapeutic effects of docosahexaenoic acid on oestrogen/androgen-induced benign prostatic hyperplasia in rats. United States: N. p., 2016. Web. doi:10.1016/J.YEXCR.2015.03.026.
Wang, Chao, Luo, Fei, Zhou, Ying, Du, Xiaoling, Shi, Jiandang, Zhao, Xiaoling, Xu, Yong, Zhu, Yan, Hong, Wei, E-mail: hongwei@tijmu.edu.cn, & Zhang, Ju, E-mail: zhangju@nankai.edu.cn. The therapeutic effects of docosahexaenoic acid on oestrogen/androgen-induced benign prostatic hyperplasia in rats. United States. doi:10.1016/J.YEXCR.2015.03.026.
Wang, Chao, Luo, Fei, Zhou, Ying, Du, Xiaoling, Shi, Jiandang, Zhao, Xiaoling, Xu, Yong, Zhu, Yan, Hong, Wei, E-mail: hongwei@tijmu.edu.cn, and Zhang, Ju, E-mail: zhangju@nankai.edu.cn. 2016. "The therapeutic effects of docosahexaenoic acid on oestrogen/androgen-induced benign prostatic hyperplasia in rats". United States. doi:10.1016/J.YEXCR.2015.03.026.
@article{osti_22648592,
title = {The therapeutic effects of docosahexaenoic acid on oestrogen/androgen-induced benign prostatic hyperplasia in rats},
author = {Wang, Chao and Luo, Fei and Zhou, Ying and Du, Xiaoling and Shi, Jiandang and Zhao, Xiaoling and Xu, Yong and Zhu, Yan and Hong, Wei, E-mail: hongwei@tijmu.edu.cn and Zhang, Ju, E-mail: zhangju@nankai.edu.cn},
abstractNote = {Benign prostatic hyperplasia (BPH) is one of the major disorders of the urinary system in elderly men. Docosahexaenoic acid (DHA) is the main component of n-3 polyunsaturated fatty acids (n-3 PUFAs) and has nerve protective, anti-inflammatory and tumour-growth inhibitory effects. Here, the therapeutic potential of DHA in treating BPH was investigated. Seal oil effectively prevented the development of prostatic hyperplasia induced by oestradiol/testosterone in a rat model by suppressing the increase of the prostatic index (PI), reducing the thickness of the peri-glandular smooth muscle layer, inhibiting the proliferation of both prostate epithelial and stromal cells, and downregulating the expression of androgen receptor (AR) and oestrogen receptor α (ERα). An in vitro study showed that DHA inhibited the growth of the human prostate stromal cell line WPMY-1 and the epithelial cell line RWPE-1 in a dose- and time-dependent manner. In both cell lines, the DHA arrested the cell cycle in the G2/M phase. In addition, DHA also reduced the expression of ERα and AR in the WPMY-1 and RWPE-1 cells. These results indicate that DHA inhibits the multiplication of prostate stromal and epithelial cells through a mechanism that may involve cell cycle arrest and the downregulation of ERα and AR expression. - Highlights: • Seal oil prevents oestradiol/testosterone (E2/T)-induced BPH in castrated rats. • Seal oil downregulates the expression of oestrogen receptor α(ERα) and androgen receptor (AR) in rat BPH tissues. • DHA inhibits the growth of human prostate stromal and epithelial cells in vitro. • DHA arrests human prostate stromal and epithelial cells in the G2/M phase and downregulates the expression of cyclin B1. • DHA inhibits the expression of ERα and AR in human prostate stromal and epithelial cells.},
doi = {10.1016/J.YEXCR.2015.03.026},
journal = {Experimental Cell Research},
number = 2,
volume = 345,
place = {United States},
year = 2016,
month = 7
}
  • The metabolism of (1,2,6,7-3H)testosterone was assessed in fibroblast monolayers derived from tissue of 5 prostates with benign hyperplasia (BPH), 4 prostates with carcinoma (PC), and 3 biopsy samples of skin, 2 nongenital skin (NG) and 1 genital skin. The following metabolites could be identified: androstanedione androstenedione, dihydrotestosterone, androsterone, epiandrosterone, androstane-3 alpha, 17 beta-diol and androstane-3 beta, 17 beta-diol. Testosterone was metabolized much more rapidly in fibroblasts originating from prostatic tissue than in fibroblasts derived from NG. A significantly higher formation of 5 alpha-androstanes and 3 alpha-hydroxysteroids could be observed in fibroblasts from BPH as compared to PC. 17-ketosteroid formation exceededmore » 5 alpha-androstane formation in BPH, whereas 5 alpha-reduction was the predominant pathway in fibroblasts grown from PC and NG. Since testosterone metabolism in fibroblasts of prostatic origin therefore resembles in many aspects that in whole prostatic tissue, fibroblasts grown from prostatic tissues might be a valuable tool for further investigation of the pathogenesis of human BPH and PC.« less
  • Symptomatic benign prostatic hyperplasia (BPH) typically occurs in the sixth and seventh decades, and the most frequent obstructive urinary symptoms are hesitancy, decreased urinary stream, sensation of incomplete emptying, nocturia, frequency, and urgency. Various medications, specifically 5-{alpha}-reductase inhibitors and selective {alpha}-blockers, can decrease the severity of the symptoms secondary to BPH, but prostatectomy is still considered to be the traditional method of management. We report the preliminary results for two patients with acute urinary retention due to BPH, successfully treated by prostate artery embolization (PAE). The patients were investigated using the International Prostate Symptom Score, by digital rectal examination, urodynamicmore » testing, prostate biopsy, transrectal ultrasound (US), and magnetic resonance imaging (MRI). Uroflowmetry and postvoid residual urine volume complemented the investigation at 30, 90, and 180 days after PAE. The procedure was performed under local anesthesia; embolization of the prostate arteries was performed with a microcatheter and 300- to 500-{mu}m microspheres using complete stasis as the end point. One patient was subjected to bilateral PAE and the other to unilateral PAE; they urinated spontaneously after removal of the urethral catheter, 15 and 10 days after the procedure, respectively. At 6-month follow-up, US and MRI revealed a prostate reduction of 39.7% and 47.8%, respectively, for the bilateral PAE and 25.5 and 27.8%, respectively, for the patient submitted to unilateral PAE. The early results, at 6-month follow-up, for the two patients with BPH show a promising potential alternative for treatment with PAE.« less
  • PurposeThis study was designed to describe the clinical, laboratorial, and urodynamic findings of prostatic artery embolization (PAE) in patients with urinary retention due to benign prostatic hyperplasia (BPH).MethodsA prospective study of 11 patients with urinary retention due to BPH was conducted. Patients underwent physical examination, prostate specific antigen (PSA) measurement, transrectal ultrasound, and magnetic resonance imaging. International prostate symptom score (IPSS), quality of life (QoL), and urodynamic testing were used to assess the outcome before and after 1 year.ResultsClinical success was 91 % (10/11 patients) with a mean follow-up of 22.3 months (range, 12-41 months). At the first year follow-up,more » the mean IPSS score was 2.8 points (p = 0.04), mean QoL was 0.4 points (p = 0.001), mean PSA decreased from 10.1 to 4.3 ng/mL (p = 0.003), maximum urinary flow (Qmax) improved from 4.2 to 10.8 mL/sec (p = 0.009), and detrusor pressure (Pdet) decreased from 85.7 to 51.5 cm H{sub 2}O (p = 0.007). Before PAE, Bladder Outlet Obstruction Index (BOOI) showed values >40 in 100 % of patients. After PAE, 30 % of patients were >40 (obstructed), 40 % were between 20 and 40 (undetermined), and 30 % were <20 (unobstructed). Patients with a BOOI <20 had higher PSA values at 1-day after PAE.ConclusionsClinical and urodynamic parameters improved significantly after PAE in patients with acute urinary retention due to BPH. Total PSA at day 1 after PAE was higher in patients with unobstructed values in pressure flow studies.« less
  • Prostatic artery embolization (PAE) has emerged as an alternative to surgical treatments for benign prostatic hyperplasia (BPH). Patient selection and refined technique are essential for good results. Urodynamic evaluation and magnetic resonance imaging are very important and technical limitations are related to elderly patients with tortuous and atherosclerotic vessels, anatomical variations, difficulty visualizing and catheterizing small diameter arteries feeding the prostate, and the potential risk of bladder and rectum ischemia. The use of small-diameter hydrophilic microcatheters is mandatory. Patients can be treated safely by PAE with low rates of side effects, reducing prostate volume with clinical symptoms and quality ofmore » life improvement without urinary incontinence, ejaculatory disorders, or erectile dysfunction. A multidisciplinary approach with urologists and interventional radiologists is essential to achieve better results.« less
  • Rationale of prostatic artery embolization (PAE) in the treatment of symptomatic benign prostatic hyperplasia is conventionally believed to include two parts: shrinkage of the enlarged prostate gland as a result of PAE-induced ischemic infarction and potential effects to relax the increased prostatic smooth muscle tone by reducing the number and density of α{sub 1}-adrenergic receptor in the prostate stroma. This review describes new insights into the likely mechanisms behind PAE, such as ischemia-induced apoptosis, apoptosis enhanced by blockage of androgens circulation to the embolized prostate, secondary denervation following PAE, and potential effect of nitric oxide pathway immediately after embolization. Studiesmore » on therapeutic mechanisms in PAE may shed light on potentially new treatment strategies and development of novel techniques.« less