Possible role of vitamins C and E co-administration in the prevention of testicular ischemia–reperfusion injury following surgical repair of torsion of the testis

Torsion of the testis (TT) is a recognised urological emergency whereby twisting of the spermatic cord causes testicular ischemia. Surgical detorsion restores perfusion, but inevitably results in testicular ischemia-reperfusion injury (tIRI). The resultant of this is oxidative stress, inflammation, impaired steroidogenesis, and a loss of spermatogenic function. Although single-agent antioxidants have been evaluated by previous studies in the mitigation of tIRI, there is limited evidence that addresses the additive or synergistic protection of co-administration of vitamins C and E after detorsion. Mechanistic data indicate possible complementary actions of vitamin E's (α-tocopherol) protection of membrane lipids from peroxidation and vitamin C's (ascorbate) clearance of aqueous reactive oxygen species, which regenerates oxidized α-tocopherol back to its active form. Together, they reduce lipid peroxidation markers, attenuate neutrophil-mediated oxidative bursts, suppress NF-κB-driven pro-inflammatory signalling, and may activate cytoprotective pathways such as Nrf2/HO-1. Preclinical studies show more consistent reductions in oxidative damage and inflammatory markers with combined treatment than with either vitamin alone. However, most evidence derives from animal and <i>in vitro</i> models. Hence, heterogeneity in dosing, timing (pre- vs. post-treatment), and outcome measures limits direct clinical translation. This review, therefore, examines preclinical and mechanistic studies of vitamins C and E co-administration in models of tIRI and related ischemic injuries.