Antioxidant Strategies in Testicular Ischemia–Reperfusion Injury—Translational Insights and Clinical Implications for Testicular Torsion Management

Testicular torsion is a time-critical urological emergency in which surgical detorsion, the only accepted treatment, simultaneously rescues and injures the gonad. Restoration of blood flow triggers a burst of reactive oxygen and nitrogen species, neutrophil recruitment, inflammasome activation, and regulated germ cell death, so that a substantial proportion of anatomically salvaged testes still undergo atrophy and functional loss. A large experimental literature, running to several hundred reports, has shown that antioxidants of almost every chemical class attenuate this injury in rodent models, yet no antioxidant has entered routine clinical use as an adjunct to detorsion in humans, and we are not aware of any adequately powered randomized trial in this setting. This narrative review integrates the redox pathophysiology of testicular ischemia–reperfusion injury with an appraisal of the agents tested against it, and then asks why the translational gap has proved so durable. We examine model heterogeneity, the dominance of pretreatment designs that cannot be reproduced in an emergency department, the reliance on short-term surrogate biochemistry rather than fertility endpoints, and the sobering precedents of neuroprotection and cardioprotection. We close with a roadmap for first-in-human evaluation, covering candidate prioritization, route and timing of administration, biomarker selection, and a feasible trial architecture.