Morteza Ghasemnejad-Berenji1,2,3, Mahmoud Ghazi-Khansari1, Iraj Yazdani1,2, Seyed Soheil Saeedi Saravi1,2,4, Maliheh Nobakht5, Alireza Abdollahi6, Javad Mohajer Ansari5, Hojjat Ghasemnejad-Berenji6, Sarvin Pashapour7, Ahmad Reza Dehpour1,2. 1. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. 2. Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran. 3. Department of Pharmacology, Faculty of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran. 4. Department of Pharmacology, Faculty of Pharmacy, Guilan University of Medical Sciences, Rasht, Iran. 5. Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. 6. Department of Pathology, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran. 7. Department of Anatomy and Reproductive Biology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Abstract
OBJECTIVES: 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 720° 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.
OBJECTIVES: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 720° 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.
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