Rapamycin protects testes against germ cell apoptosis and oxidative stress induced by testicular ischemia-reperfusion

Objective(s):Rapamycin is an immunosuppressant compound with a broad spectrum of pharmaco-logical activities. In recent years, it has been used successfully to decrease ischemia-reperfusion injury in several organ systems. The purpose of the present study was to examine the effect of rapamycin on testicular ischemia-reperfusion injury. Materials and Methods: Seventy-two adult male Wistar rats were divided into six groups: control (group۱), sham-operated (Group۲), T/D + DMSO as vehicle group (group۳), and groups ۴–۶; respectively received ۰.۵, ۱, and ۱.۵ mgkg-۱ of rapamycin , IP ۳۰ min before detorsion. Ischemia was achieved by twisting the right testis ۷۲۰o clockwise for ۱ hr. The right testis of ۶ animals from each group were excised ۴ hr after detorsion for the measurement of lipid peroxidation, caspase-۳, and antioxidant enzyme activities. Histopathological changes and germ cell apoptosis were determined by measuring mean of seminiferous tubules diameters (MSTD) and TUNEL test in right testis of ۶ animals per group, ۲۴ hr after detorsion. Results: Testicular T/D caused increases in the apoptosis, malondialdehyde (MDA), and caspase-۳ levels and decreases in the superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities in ipsilateral testis (P<۰.۰۰۱). The rats treated with rapamycin had significant decreases in the MDA and caspase-۳ levels and significant increases in the SOD, CAT and GPx activities in ipsilateral testis compared with the T/D group (P<۰.۰۰۱); germ cell apoptosis was decreased, and MSTD was improved. Conclusion: Rapamycin administration during testicular torsion decreased ischemia/reperfusion (I/R) cellular damage.

Keywords:

Apoptosis , Ischemia-reperfusion , Rapamycin , Testicular torsion , Testis