Comparison of multiple doses of cyclosporine A on germ cell apoptosis and epididymal sperm parameters after testicular ischemia/reperfusion in rats

• Published in: Experimental and molecular pathology Vol. 110; p. 104271
• Main Authors: Yazdani, Iraj, Majdani, Raheleh, Ghasemnejad-berenji, Morteza, Dehpour, Ahmad Reza
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.10.2019
• Subjects: Animals; Apoptosis; Apoptosis - drug effects; Caspase 3 - metabolism; Catalase - metabolism; Cyclosporine - pharmacology; Cyclosporine A; Epididymis - drug effects; Epididymis - metabolism; Epididymis - pathology; Germ cell; Germ Cells; Glutathione Peroxidase - metabolism; Immunosuppressive Agents - pharmacology; Male; Malondialdehyde - metabolism; Mitochondrial permeability transition pore; Oxidative Stress - drug effects; Rats, Wistar; Reperfusion Injury - physiopathology; Spermatic Cord Torsion - physiopathology; Spermatozoa - drug effects; Spermatozoa - pathology; Superoxide Dismutase - metabolism; Testicular T/D; Testis - blood supply; Testis - drug effects; Testis - metabolism; Germ cell; Cyclosporine A; Mitochondrial permeability transition pore; Testicular T/D; Apoptosis
• ISSN: 0014-4800; 1096-0945
• DOI: 10.1016/j.yexmp.2019.104271

Testicular torsion/detorsion (T/D) is an inflammatory problem in men genital system with infertility effects. Cyclosporine A (CsA) as an immunosuppressant medication, exerts anti-inflammatory properties in tissue injuries. We sought to compare the efficacy of 3 doses of CsA on oxidative stress, apoptosis and epididymal sperm quality after ipsilateral testicular T/D. 96 mature male rats were divided into six groups 16 each in: Control group (Group1), Sham operated (Group2), In rest groups, the right testis was twisted 720° in a clockwise direction for 1 h; T/D + 0.1% dimethylsulfoxide) DMSO((Group3), and in groups 4–6; CsA were administered 1, 5, and 10 mg/kg, intravenously (iv) 30 and 90 min after torsion, respectively. Tissue malondialdehyde (MDA) level and caspase-3 activity increased and catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities decreased in compared with control group 4 h after detorsion (p < .001). In six rats of each group 24 h after detorsion, histopathological changes and germ cell apoptosis were significantly deteriorated by determining mean of seminiferous tubules diameters (MSTD) and TUNEL assay. Moreover, 30 days after T/D, sperm concentration and motility were examined in rest of animals. Pre- and post-reperfusion CsA diminished MDA and caspase-3levels and normalized antioxidant enzymes activities. Germ cell apoptosis was significantly reduced, as well as, MSTD and long-term sperm insults were improved. Inhibition of mitochondrial permeability transition pore opening is suggested mechanism for cell protection against testicular T/D insults.