Establishment of a Preclinical Model of Benign Prostatic Hyperplasia in Male Rats and Evaluation of a Next-Generation Anti-Inflammatory Therapy through Detailed Histopathology

Introduction: This study aimed to establish a reproducible preclinical rat model of BPH that integrates hormonal stimulation with chronic inflammatory signaling and to evaluate the therapeutic efficacy of a next-generation anti-inflammatory compound (NGI-۱۰۱) using comprehensive histopathological and molecular analyses.Methods: Forty adults male Wistar rats were randomly assigned to four experimental groups: control, BPH model, BPH treated with NGI-۱۰۱, and BPH treated with finasteride. BPH was induced via subcutaneous testosterone propionate combined with intermittent low-dose lipopolysaccharide administration over six weeks. Prostate volume was assessed longitudinally, while histopathological alterations were evaluated using Hematoxylin–Eosin (H&E) and Masson’s trichrome staining. Prostatic inflammatory cytokines (IL-۶ and TNF-α) were quantified using ELISA.Results: The induction protocol showed that prostate volume significantly increased in the treated group compared to the control group (+۲۱۲.۴% ± ۱۲.۳; P-value<۰.۰۰۱) accompanied by marked epithelial and stromal hyperplasia and elevated inflammatory cytokine levels. Treatment with NGI-۱۰۱ significantly reduced prostate volume (−۴۲% vs. BPH, P-value<۰.۰۰۱), attenuated histopathological severity scores, and normalized IL-۶ and TNF-α expression more effectively than Finasteride. Histological evaluation revealed substantial restoration of glandular architecture and reduced stromal fibrosis in the NGI-۱۰۱ group.Conclusion: This study presents a translationally relevant rat model of BPH that closely mirrors the inflammatory and histopathological features of human disease. The pronounced therapeutic effects of NGI-۱۰۱ highlight inflammation-targeted strategies as a promising avenue for future BPH management.

کلیدواژه ها:

benign prostatic hyperplasia ، preclinical model ، chronic inflammation ، histopathology ، anti-inflammatory therapy ، Translational Urology