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Background <p>Testicular ischemia reperfusion injury (TIRI) remains a significant etiological factor in male infertility. In this study, we evaluated the ameliorative potential of febuxostat, amlodipine, and vitamin E against testicular ischemia-reperfusion injury in male Wistar rats. </p> Method <p>Fifty-four (54) male Wistar rats were grouped into nine (n = 6): Sham (SO), Torsion + Detorsion (TD), Torsion + Febuxostat + Detorsion (TFD), TD + Amlodipine (TDA), TD + Vitamin E (TDV), TFD + Amlodipine (TFDA), TFD + Vitamin E (TFDV), TDA + Vitamin E (TDAV), and TFDA + Vitamin E (TFDAV). On day 52, two estrus-confirmed female rats were introduced per selected male for fertility assessment, with cohabitation allowed for 72 h. Blood samples (hormonal assays), left testis (biochemical assays and mRNA expression of spermatogenic genes), and epididymis (sperm indices) were collected on day 57 after detorsion. </p> Result <p>The TD group showed significant disruptions in testicular oxidative milieu (P &lt; 0.001). There was also significant inflammatory activation (TLR4, TNF-α, and MPO), and apoptosis (caspase-3, DNA fragmentation) progressed significantly (P &lt; 0.001). This resulted in hormonal disruptions and reduced germ cell counts. Moreover, we observed significant downregulation of key spermatogenic genes (KIT, RHCG, NDRG4), with dysregulated expression of others (LGALS, LRRC34). Notably, TFDAV robustly reversed the debilitating effects of TD and preserved testicular function compared to other treatment regimens. Although the TFDAV group displayed paradoxical gene expression profiles, the recovery of fertility and histological restoration suggest that spermatogenic recovery still proceeded via compensatory pathways. </p> Conclusion <p>Conclusively, this study presents a multi-target approach for managing male infertility.</p>

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Timing-Dependent Modulation of Testicular Ischemia–Reperfusion Injury by Febuxostat, Amlodipine and Vitamin E

  • 期刊论文

  • 发表日期：

    2026年7月14日

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  • Richard Adedamola Ajike,
  • Oluwaseun Samuel Hezekiah,
  • Bamidele Oluwole Olusola,
  • Sodiq Opeyemi Hammed,
  • Olubunmi Simeon Oyekunle,
  • Waidi Adeoye Saka,
  • Gbenga Opeyemi Owolabi,
  • Oluwatobi Sunday Ajiroba,
  • Oreoluwa Janet Adedeji,
  • Olajumoke Deborah Ogunleye,
  • Babatunde Alabi Adebola,
  • Oladele Ayobami Afolabi

摘要

Background

Testicular ischemia reperfusion injury (TIRI) remains a significant etiological factor in male infertility. In this study, we evaluated the ameliorative potential of febuxostat, amlodipine, and vitamin E against testicular ischemia-reperfusion injury in male Wistar rats.

Method

Fifty-four (54) male Wistar rats were grouped into nine (n = 6): Sham (SO), Torsion + Detorsion (TD), Torsion + Febuxostat + Detorsion (TFD), TD + Amlodipine (TDA), TD + Vitamin E (TDV), TFD + Amlodipine (TFDA), TFD + Vitamin E (TFDV), TDA + Vitamin E (TDAV), and TFDA + Vitamin E (TFDAV). On day 52, two estrus-confirmed female rats were introduced per selected male for fertility assessment, with cohabitation allowed for 72 h. Blood samples (hormonal assays), left testis (biochemical assays and mRNA expression of spermatogenic genes), and epididymis (sperm indices) were collected on day 57 after detorsion.

Result

The TD group showed significant disruptions in testicular oxidative milieu (P < 0.001). There was also significant inflammatory activation (TLR4, TNF-α, and MPO), and apoptosis (caspase-3, DNA fragmentation) progressed significantly (P < 0.001). This resulted in hormonal disruptions and reduced germ cell counts. Moreover, we observed significant downregulation of key spermatogenic genes (KIT, RHCG, NDRG4), with dysregulated expression of others (LGALS, LRRC34). Notably, TFDAV robustly reversed the debilitating effects of TD and preserved testicular function compared to other treatment regimens. Although the TFDAV group displayed paradoxical gene expression profiles, the recovery of fertility and histological restoration suggest that spermatogenic recovery still proceeded via compensatory pathways.

Conclusion

Conclusively, this study presents a multi-target approach for managing male infertility.