Uroprotective effect of diarylpropionitrile versus finasteride on rat model of testosterone-induced prostatic hyperplasia.

Abstract

Benign prostatic hyperplasia (BPH) is a common public health problem in ageing men worldwide. Diarylpropionitrile, a selective ERβ agonist, favorably regulates cell proliferation and inflammation, two major hallmarks of BPH pathology. This study aimed to explore the mitigative impact of diarylpropionitrile on testosterone-driven BPH in rats. 40 Sprague Dawley male rats aged 2.5-3 months were randomly divided into 4 groups (n = 10): a normal control group, a testosterone-induced BPH group, a finasteride-treated group, and a diarylpropionitrile-treated group. BPH was induced by daily subcutaneous testosterone injections for 4 weeks, with finasteride and diarylpropionitrile administered orally once daily for the same duration, one hour before each testosterone injection. After 4 weeks of treatment, macroscopic and microscopic features of prostatic hyperplasia and androgenic, proliferative, angiogenic, apoptotic, and inflammatory biomarkers in prostatic tissue homogenates were assessed. Testosterone administration significantly increased prostate weight, prostatic index, and hyperplasia scores, while treatment with either diarylpropionitrile or finasteride effectively ameliorated these testosterone-induced changes. Both treatments significantly lowered elevated prostatic DHT, 5αR2, β-catenin, and PCNA levels, demonstrating a strong anti-proliferative effect. They also attenuated the increased pro-inflammatory cytokines IL-6, IL-27, and PGE2 and growth factors TGF-β and VEGF. Furthermore, both agents inhibited testosterone-induced ERβ upregulation and increased expression of the anti-apoptotic protein BCL2. There were no substantial differences comparing finasteride and diarylpropionitrile in the majority of the tested parameters. Diarylpropionitrile alleviates testosterone-driven BPH in rats by modulating key pathways associated with cellular proliferation and inflammation. Diarylpropionitrile, as an ERβ agonist, represents a promising alternative for the BPH treatment through multi-targeted mechanisms.