Aljorani Randa Hisham, Al-Zubaidy Adeeb Ahmed, Abdali Nibrass Taher
Department of Pharmacology, College of Medicine, Al-Nahrain University, Baghdad, Iraq.
Department of Pharmacology, College of Medicine, University of Warith Al-Anbiyaa, Karbalaa, Iraq.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Apr 29. doi: 10.1007/s00210-025-04215-7.
Benign prostatic hyperplasia (BPH) is the most common urological condition among elderly men. Because of modifiable metabolic risk factors, the prevalence of BPH is rising. This study aimed to investigate the therapeutic potential of ripasudil, a Rho kinase inhibitor, and also its combination with finasteride in attenuating testosterone-induced BPH in male Wistar rats. Rats were given testosterone propionate (3 mg/kg/day) for 4 weeks to develop BPH and were treated with ripasudil (3 mg/kg/day), finasteride (5 mg/k/day), or a combination of both concomitant the testosterone injection throughout the course of the study. The results revealed a significant increase in prostate index, a rise in prostate-specific antigen (PSA), and characteristic histopathological changes indicative of BPH post-testosterone administration. Additionally, testosterone induced elevation in inflammatory markers (interleukin-6 (IL-6), interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta (TGF-β), and nuclear factor-κB (NF-κB)), oxidative stress (increase in malondialdehyde (MDA) and decrease in glutathione (GSH)), and elevation of Rho kinase1 (ROCK1). However, intervention with ripasudil or its combination with finasteride effectively mitigated these changes possibly via anti-inflammatory, antioxidative, and ROCK inhibition properties. These findings highlight the potential of ripasudil as adjunctive therapies for BPH, offering an approach for targeting inflammation, oxidative stress, and ROCK pathways. Further research is needed to clarify the underlying mechanisms driving these therapeutic effects and validate these findings in clinical settings.
良性前列腺增生（BPH）是老年男性中最常见的泌尿系统疾病。由于存在可改变的代谢风险因素，BPH的患病率正在上升。本研究旨在探讨Rho激酶抑制剂ripasudil及其与非那雄胺联合使用对减轻雄性Wistar大鼠睾酮诱导的BPH的治疗潜力。给大鼠注射丙酸睾酮（3mg/kg/天）持续4周以诱导BPH，并在整个研究过程中同时给予ripasudil（3mg/kg/天）、非那雄胺（5mg/k/天）或两者的组合，同时注射睾酮。结果显示，睾酮给药后前列腺指数显著增加、前列腺特异性抗原（PSA）升高以及出现指示BPH的特征性组织病理学变化。此外，睾酮诱导炎症标志物（白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）、转化生长因子-β（TGF-β）和核因子-κB（NF-κB））升高、氧化应激（丙二醛（MDA）增加和谷胱甘肽（GSH）减少）以及Rho激酶1（ROCK1）升高。然而，ripasudil或其与非那雄胺的联合干预可能通过抗炎、抗氧化和ROCK抑制特性有效减轻了这些变化。这些发现突出了ripasudil作为BPH辅助治疗的潜力，为针对炎症、氧化应激和ROCK途径提供了一种方法。需要进一步研究以阐明驱动这些治疗效果的潜在机制，并在临床环境中验证这些发现。
