POTENTIAL THERAPEUTIC TARGETS IN THE PREVENTION OF TESTICULAR ISCHEMIA REPERFUSION INJURY (TIRI)

Richard Adedamola Ajike¹Ayodeji Folorunsho Ajayi¹Olubunmi Simeone Oyekunle¹Waidi Adeoye Saka¹Opeyemi Hammed¹Oreoluwa Janet Adedeji¹Olajumoke Deborah Ogunleye¹Oluwaseun Samuel Hezekiah^1*Oluwakemi Victoria Olayinka-Akinpelu¹Babatunde Adebola Alabi²DAVID ISHOLA³Oladele Ayobami Afolabi^1*

• ¹Ladoke Akintola University of Technology, Ogbomosho, Nigeria
• ²University of Pretoria, Pretoria, South Africa
• ³Kings University, Ode Omu, Nigeria

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.