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Nortriptyline protects testes against germ cell apoptosis and oxidative stress induced by testicular ischaemia/reperfusion
Authors:I. Yazdani  M. Ghazi‐Khansari  S. S. Saeedi Saravi  M. Nobakht  R. Majdani  S. M. Rezayat  S. E. Mousavi  A. Yari  A. R. Dehpour
Affiliation:1. Department of Pharmacology, School of Medicine, International Campus, Tehran University of Medical Sciences, Tehran, Iran;2. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran;3. Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran;4. Department of Toxicology‐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 cellular and molecular biology, Faculty of Basic Science, University of Maragheh, Maragheh, Iran;7. Department of Toxicology‐Pharmacology, Faculty of Pharmacy, Pharmaceutical Science Branch, Islamic Azad University (IAUPS), Tehran, Iran;8. Department of Anatomy, School of Medicine, Alborz University of Medical Science, Karaj, Iran
Abstract:We designed this experiment to evaluate the effects of nortriptyline on testicular injury after torsion/detorsion (T/D). Ninety‐six adult Wistar rats were divided into six groups 16 each in control group (Group 1), sham operated (Group 2), T/D + saline (Group 3), and in groups 4–6; were administered 2, 10 and 20 mg kg?1, i.p. of nortriptyline 30 and 90 min after torsion respectively. Testicular torsion was created by twisting the right testis 720° in clockwise direction for 1 h. In six rats of each group, tissue MDA level and caspase‐3 activity increased and the activities of catalase, superoxide dismutase and glutathione peroxidase decreased in compared with control group 4 h after detorsion (P < 0.001). In six rats of each group 24 h after detorsion, histopathological changes and germ cell apoptosis were significantly deteriorated by measuring mean of seminiferous tubules diameters (MSTD) and TUNEL test. Moreover, 30 days after T/D, sperm concentration and motility were examined in rest of rats. Pre‐ and post‐reperfusion nortriptyline could reduce MDA and caspase‐3 levels and normalise antioxidant enzymes activities, dose dependently. Germ cell apoptosis was significantly decreased, and the MSTD, as well as sperm functions, were significantly improved. Inhibition of mitochondrial permeability transition pore is probably involved in protective effects of nortriptyline against testicular T/D cell damages.
Keywords:Apoptosis     mitochondrial permeability transition pore     nortriptyline  oxidative stress  testicular T/D
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