2‐Methoxyestradiol Attenuates Testosterone‐Induced Benign Prostate Hyperplasia in Rats through Inhibition of HIF‐1α/TGF‐β/Smad2 Axis

Abstract

Benign prostatic hyperplasia (BPH) is a common disorder in the male population. 2-Methoxyestradiol (2ME) is an end metabolite of estrogens with pleiotropic pharmacological properties. This study aimed to explore the potential ameliorative effects of 2ME against testosterone-induced BPH in rats. 2-Methoxyestradiol (50 and 100 mg/kg, dissolved in DMSO) prevented the rise in prostatic index and weight in comparison to testosterone-alone-treated animals for 2 weeks. Histological examination indicated that 2ME ameliorated pathological changes in prostate architecture. This was confirmed by the ability of 2ME to decrease the glandular epithelial height when compared to the testosterone group. Also, 2ME improved testosterone-induced oxidative stress as it inhibited the rise in lipid peroxide content and the exhaustion of superoxide dismutase (SOD) activity. The beneficial effects of 2ME against the development of BPH were substantiated by assessing proliferation markers, preventing the rise in cyclin D1 protein expression and enhancing Bax/Bcl2 mRNA ratio. It significantly reduced prostate content of tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), nuclear factor κB (NF-κB), and transforming growth factor β (TGF-β). In addition, 2ME reduced hypoxia-inducible factor 1-α (HIF-1α) and phospho-Smad2 (p-Smad2) protein expression compared to the testosterone group. In conclusion, 2ME attenuates experimentally induced BPH by testosterone in rats through, at least partly, inhibition of HIF-1α/TGF-β/Smad2 axis.

Piceatannol Attenuates Testosterone-Induced Benign Prostatic Hyperplasia in Rats by Modulation of Nrf2/HO-1/NFκB Axis

“…Cyclin D1 is involved in regulating cell proliferation and its abundance is commonly interpreted in favor of cell division ( Fu et al, 2004 ). In line with previous studies ( Abdel-Naim et al, 2018 ; Basha et al, 2019 ), our data indicated that testosterone significantly enhanced cyclin D1 expression. However, PIC SNEDDS successfully hampered the raised cyclin D1 expression as detected immunohistochemically.…”

RETRACTED: Attenuation of Benign Prostatic Hyperplasia by Optimized Tadalafil Loaded Pumpkin Seed Oil-Based Self Nanoemulsion: In Vitro and In Vivo Evaluation

“…The normal group (group 1) was not administered any treatment or testosterone. The remaining five groups were treated with 3 mg/kg testosterone enanthate subcutaneously (SC) five days a week for two weeks for BPH induction [35]. One control group (group 2) only received 3 mg/kg testosterone enanthate subcutaneously (SC) five days a week for two weeks.…”

[Retracted] Periodontitis Exacerbates Benign Prostatic Hyperplasia through Regulation of Oxidative Stress and Inflammation

“…Oxidative stress has been highly associated with the onset of several inflammatory pathologies occurring in elderly people, including periodontitis, osteoporosis, and metabolic disorders [12,15,16]. Also, clinical and experimental studies have a confirmed oxidative stress as a key contributor to the pathogenesis of BPH [17][18][19][20]. Moreover, compensatory cellular proliferation may be triggered by oxidative stress, which eventually leads to the growth of hyperplastic prostate tissue, whereas the factors that induce a more oxidative state in the prostate remain unclear.…”