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

Document Type: Original Article

Authors

1 Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences

2 Experimental Medicine Research Center, Tehran University of Medical Sciences

3 Department of Pharmacology, Faculty of Pharmacy, Urmia University of Medical Sciences

4 Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

5 Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran

6 Department of Pharmacology, Faculty of Pharmacy, Guilan University of Medical Sciences, Rasht, Iran

7 Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

8 Department of Pathology, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran

9 Department of Anatomy and Reproductive Biology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

10 Department of Pathology, Urmia University of Medical Sciences, Urmia, Iran

Abstract

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 (group1), sham-operated (Group2), T/D + DMSO as vehicle group (group3), and groups 4–6; respectively received 0.5, 1, and 1.5 mgkg-1 of rapamycin , IP 30 min before detorsion. Ischemia was achieved by twisting the right testis 720o clockwise for 1 hr. The right testis of 6 animals from each group were excised 4 hr after detorsion for the measurement of lipid peroxidation, caspase-3, 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 6 animals per group, 24 hr after detorsion.
Results: Testicular T/D caused increases in the apoptosis, malondialdehyde (MDA), and caspase-3 levels and decreases in the superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities in ipsilateral testis (P<0.001). The rats treated with rapamycin had significant decreases in the MDA and caspase-3 levels and significant increases in the SOD, CAT and GPx activities in ipsilateral testis compared with the T/D group (P<0.001); germ cell apoptosis was decreased, and MSTD was improved.
Conclusion: Rapamycin administration during testicular torsion decreased ischemia/reperfusion (I/R) cellular damage.

Keywords


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