Ripasudil, a Rho kinase inhibitor, attenuates testosterone-induced benign prostatic hyperplasia in rats: targeting inflammation, oxidative stress, and Rho kinase pathways.

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.