AUTHOR=Ajike Richard Adedamola , Ajayi Ayodeji Folorunsho , Oyekunle Olubunmi Simeon , Saka Waidi Adeoye , Hammed Sodiq Opeyemi , Adedeji Oreoluwa Janet , Ogunleye Olajumoke Deborah , Hezekiah Oluwaseun Samuel , Olayinka-Akinpelu Oluwakemi Victoria , Alabi Babatunde Adebola , Ajao Ishola David , Afolabi Oladele Ayobami 

TITLE=Potential therapeutic targets in the prevention of testicular ischemia-reperfusion injury

JOURNAL=Frontiers in Reproductive Health

VOLUME=Volume 7 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/reproductive-health/articles/10.3389/frph.2025.1706914

DOI=10.3389/frph.2025.1706914

ISSN=2673-3153

ABSTRACT=Testicular ischemia-reperfusion injury (TIRI) is the outcome of the repair of torsion of the testis. It has been reported to cause loss of testicular function in both the ipsilateral and contralateral testes in the long run, thus resulting in male infertility. Its prevention is complex due to activation of oxidative stress, inflammation and apoptotic pathways in the ischemic and reperfusion phases. Previous experimental studies have successfully mitigated TIRI by applying ischemic preconditioning, ischemic postconditioning and pre-treatment regimens, which may not be appropriate for humans due to limitations associated with their application in real-life situations. However, pharmacological postconditioning, which involves the use of drugs to block key points in the TIRI pathway, can be proactively applied in humans, offering a better TIRI management strategy. Pathophysiological events in the TIRI pathway include activation of: xanthine oxidase (XO)-reactive oxygen species (ROS) pathway in the ischemic phase, calcium-mediated apoptotic pathway in the early reperfusion phase, and ROS-burst in the late reperfusion phase, among others. Hence, this review recommends that blocking the XO-ROS pathway with febuxostat after the onset of testicular torsion (TT), minimizing the calcium-mediated apoptotic pathway and restoring the loss of vasomotor tone with amlodipine on reperfusion, as well as blocking ROS-burst with vitamin E in the later phase of reperfusion, may help to mitigate the effect of TIRI in humans and thus prevent future infertility. Nevertheless, further research is needed to verify this claim and delineate the possible drug-drug interactions, as well as potential effects on other organs.