Synergistic effect of rapamycin and metformin against germ cell apoptosis and oxidative stress after testicular torsion/detorsion-induced ischemia/reperfusion in rats

Ghasemnejad-berenji, M. and Ghazi-Khansari, M. and Pashapour, S. and Jafari, A. and Yazdani, I. and Ghasemnejad-berenji, H. and Saeedi Saravi, S.S. and Sadeghpour, S. and Nobakht, M. and Abdollahi, A. and mohajer Ansari, J. and Dehpour, A.R. (2018) Synergistic effect of rapamycin and metformin against germ cell apoptosis and oxidative stress after testicular torsion/detorsion-induced ischemia/reperfusion in rats. Biomedicine and Pharmacotherapy, 105. pp. 645-651.

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Abstract

The aim of this study was to investigate the effects of rapamycin (rapa) and metformin (met), combined administration on testicular torsion-detorsion (T/D) injury. A total of 108 male rats were divided randomly into six groups (n = 18), control, sham-operated, T/D, T/D + met (100 mg/kg), T/D + rapa (0.25 mg/kg) and T/D + met (100 mg/kg)+rapa (0.25 mg/kg). Except for the control and sham groups, torsion was created by rotating the right testis 720° in a clockwise direction for 1 h. Treatment groups received drug intraperitoneally, 30 min before detorsion. The right testis of 6 animals from each group was excised 4 h 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 terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate�biotin nick end labeling (TUNEL) test in rest of animals, 24 h after detorsion. In T/D group tissue malondialdehyde (MDA) level and caspase-3 activity increased and the activities of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) decreased in comparison with the control group after detorsion. Met and rapa separately pre-treatment reduced MDA and caspase-3 levels, normalized antioxidant enzyme activities, reduced germ cell apoptosis and improved the MSTD in comparison with T/D group. However combined administration of met and rapa indicated a significant augmented effect as compared to the individual drug interventions on the reversal of T/D induced oxidative stress, apoptosis, and histologic changes, suggesting a synergistic response. Thus, this study shows that rapa and met combination have significant synergistic effects against oxidative stress and apoptosis and opens up further possibilities for the design of new combinatorial therapies to prevent tissue damage after ischemia-reperfusion (I/R). © 2018 Elsevier Masson SAS

Item Type: Article
Additional Information: cited By 1
Uncontrolled Keywords: caspase 3; catalase; glutathione peroxidase; malonaldehyde; metformin; rapamycin; reduced nicotinamide adenine dinucleotide; superoxide; superoxide dismutase, animal experiment; animal model; animal tissue; antioxidant activity; apoptosis; Article; comparative study; controlled study; drug potentiation; enzyme activity; enzyme linked immunosorbent assay; germ cell; histopathology; lipid peroxidation; male; nonhuman; oxidative stress; priority journal; rat; reperfusion injury; seminiferous tubule epithelium; single drug dose; testicular torsion detorsion; testicular torsion detorsion; testis tissue; testis torsion; TUNEL assay
Subjects: WJ Urogenital System
QV Pharmacology
Depositing User: eprints admin
Date Deposited: 29 Dec 2018 06:07
Last Modified: 29 Dec 2018 06:07
URI: http://eprints.iums.ac.ir/id/eprint/5990

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