Long-term protective effect of tadalafil on spermatogenesis following testicular ischemia-reperfusion injury in a rat model

Abstract

Background: Testicular torsion is a urologic emergency that can lead to testicular atrophy and infertility owing to ischemia-reperfusion injury (IRI). The aim of this study was to evaluate the long-term protective effect of tadalafil, a phosphodiesterase-5 inhibitor used to treat erectile dysfunction, on spermatogenesis in a rat testicular model of IRI. Methods: Forty-eight adolescent Sprague–Dawley rats were divided into six groups of 8 each (A–F). Sham operation was performed on group A. Group B underwent surgical 720∘ torsion of the left testis without any medication. Groups C, D, E and F underwent surgical torsion and administration of tadalafil at varying doses (0.3 and 1.0 mg/kg) and durations (single or daily administration for four weeks). After three hours of torsion, detorsion was performed on all groups except group A. Four weeks after the operation, both testes were evaluated for spermatogenesis using the Johnsen scoring system. To evaluate the protective effect of tadalafil against oxidative stress induced by IRI, the malondialdehyde and superoxide dismutase levels of both testes were analyzed four hours after detorsion using the same experimental protocol as for groups A, B, and C. Results: Experimental groups treated with high-dose tadalafil showed higher Johnsen scores for spermatogenesis than the low-dose groups. Groups that received daily tadalafil administration for four weeks showed higher Johnsen scores than those receiving single doses. Furthermore, histopathologic findings and molecular markers related to oxidative stress were markedly improved following tadalafil administration. Conclusions: Tadalafil alleviated the oxidative stress and long-term deterioration of spermatogenesis in a rat testicular model of IRI by restoring the antioxidant status.

Keywords

• spermatic cord torsion
• ischemia-reperfusion injury
• phosphodiesterase-5 inhibitors
• animal model
• spermatogenesis