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<p>Benign prostatic hyperplasia (BPH) is a prevalent urological disorder in aging men, frequently linked to hormonal fluctuations. Agomelatine (AGO), a melatonergic receptor agonist and serotonin 2C antagonist, has demonstrated anti-inflammatory and antioxidant properties. This study aimed to explore the potential of AGO in mitigating BPH induced by testosterone propionate (TP) in rats. Male rats received TP (5&#xa0;mg/kg/day, subcutaneously) to induce BPH and were pretreated with AGO (80&#xa0;mg/kg/day) for 28&#xa0;days. AGO inhibited the rise in prostate index, serum prostate-specific antigen (PSA), and testosterone levels compared to the BPH-only group. Histological analysis revealed that AGO significantly improved the pathological alterations in prostate tissue architecture when compared to BPH-only group. Furthermore, AGO notably reduced oxidative stress induced by TP, evidenced by a decrease in lipid peroxidation and preserved levels of reduced glutathione. This reduction in oxidative stress led to a decrease in pro-inflammatory cytokines in the prostate, such as Toll-like receptor 4 (TLR4) and interleukin-1 beta (IL-1β). Additionally, AGO caused a marked decrease in of NLRP3 inflammasome and vascular endothelial growth factor-A (VEGF-A) protein expressions. When compared to the BPH group, AGO’s effects also included a reduction in the immunoexpression of nuclear factor kappa B (NF-κB) and myeloid differentiation primary response 88 (MyD88) proteins. The findings from this study provide new evidence that AGO can alleviate testosterone-induced BPH in rats, likely through the inhibition of the TLR4/NFκB and NLRP3/IL-1β signaling pathways. These results suggest that AGO could be a promising therapeutic option for managing BPH.</p> Graphical Abstract <p></p>

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Protective role of agomelatine via modulation of TLR4/NF-κB: NLRP3/IL-1β signaling pathways in testosterone-induced benign prostatic hyperplasia in rats

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月19日

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  • Asmaa Mohamed Abdel-Aziz,
  • Sara M. Ahmed,
  • Walaa Yehia Abdelzaher,
  • Nada Amgad Mohamed,
  • Alyaa E. Abdelkader,
  • Rasha Fouad Ahmed,
  • Asmaa Mohamed Mahmoud Ali,
  • Al Shimaa Mahmoud Kotb,
  • Alyaa Abdelfattah Abdelmonaem

摘要

Benign prostatic hyperplasia (BPH) is a prevalent urological disorder in aging men, frequently linked to hormonal fluctuations. Agomelatine (AGO), a melatonergic receptor agonist and serotonin 2C antagonist, has demonstrated anti-inflammatory and antioxidant properties. This study aimed to explore the potential of AGO in mitigating BPH induced by testosterone propionate (TP) in rats. Male rats received TP (5 mg/kg/day, subcutaneously) to induce BPH and were pretreated with AGO (80 mg/kg/day) for 28 days. AGO inhibited the rise in prostate index, serum prostate-specific antigen (PSA), and testosterone levels compared to the BPH-only group. Histological analysis revealed that AGO significantly improved the pathological alterations in prostate tissue architecture when compared to BPH-only group. Furthermore, AGO notably reduced oxidative stress induced by TP, evidenced by a decrease in lipid peroxidation and preserved levels of reduced glutathione. This reduction in oxidative stress led to a decrease in pro-inflammatory cytokines in the prostate, such as Toll-like receptor 4 (TLR4) and interleukin-1 beta (IL-1β). Additionally, AGO caused a marked decrease in of NLRP3 inflammasome and vascular endothelial growth factor-A (VEGF-A) protein expressions. When compared to the BPH group, AGO’s effects also included a reduction in the immunoexpression of nuclear factor kappa B (NF-κB) and myeloid differentiation primary response 88 (MyD88) proteins. The findings from this study provide new evidence that AGO can alleviate testosterone-induced BPH in rats, likely through the inhibition of the TLR4/NFκB and NLRP3/IL-1β signaling pathways. These results suggest that AGO could be a promising therapeutic option for managing BPH.

Graphical Abstract