PMID- 31251898 OWN - NLM STAT- MEDLINE DCOM- 20200225 LR - 20200225 IS - 1096-0945 (Electronic) IS - 0014-4800 (Linking) VI - 110 DP - 2019 Oct TI - Comparison of multiple doses of cyclosporine A on germ cell apoptosis and epididymal sperm parameters after testicular ischemia/reperfusion in rats. PG - 104271 LID - S0014-4800(18)30536-7 [pii] LID - 10.1016/j.yexmp.2019.104271 [doi] AB - 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. METHODS: 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 degrees 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. RESULTS: 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. CONCLUSIONS: 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. CI - Published by Elsevier Inc. FAU - Yazdani, Iraj AU - Yazdani I AD - Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. FAU - Majdani, Raheleh AU - Majdani R AD - Department of Cellular and Molecular Biology, Faculty of Basic Science, University of Maragheh, Maragheh, Iran. FAU - Ghasemnejad-Berenji, Morteza AU - Ghasemnejad-Berenji M AD - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran. FAU - Dehpour, Ahmad Reza AU - Dehpour AR AD - Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: dehpour@yahoo.com. LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190625 PL - Netherlands TA - Exp Mol Pathol JT - Experimental and molecular pathology JID - 0370711 RN - 0 (Immunosuppressive Agents) RN - 4Y8F71G49Q (Malondialdehyde) RN - 83HN0GTJ6D (Cyclosporine) RN - EC 1.11.1.6 (Catalase) RN - EC 1.11.1.9 (Glutathione Peroxidase) RN - EC 1.15.1.1 (Superoxide Dismutase) RN - EC 3.4.22.- (Caspase 3) SB - IM MH - Animals MH - Apoptosis/*drug effects MH - Caspase 3/metabolism MH - Catalase/metabolism MH - Cyclosporine/*pharmacology MH - Epididymis/*drug effects/metabolism/pathology MH - Germ Cells MH - Glutathione Peroxidase/metabolism MH - Immunosuppressive Agents/pharmacology MH - Male MH - Malondialdehyde/metabolism MH - Oxidative Stress/drug effects MH - Rats, Wistar MH - Reperfusion Injury/*physiopathology MH - Spermatic Cord Torsion/physiopathology MH - Spermatozoa/*drug effects/pathology MH - Superoxide Dismutase/metabolism MH - Testis/blood supply/*drug effects/metabolism OTO - NOTNLM OT - Apoptosis OT - Cyclosporine A OT - Germ cell OT - Mitochondrial permeability transition pore OT - Testicular T/D EDAT- 2019/06/30 06:00 MHDA- 2020/02/26 06:00 CRDT- 2019/06/29 06:00 PHST- 2018/11/11 00:00 [received] PHST- 2019/05/20 00:00 [revised] PHST- 2019/06/14 00:00 [accepted] PHST- 2019/06/30 06:00 [pubmed] PHST- 2020/02/26 06:00 [medline] PHST- 2019/06/29 06:00 [entrez] AID - S0014-4800(18)30536-7 [pii] AID - 10.1016/j.yexmp.2019.104271 [doi] PST - ppublish SO - Exp Mol Pathol. 2019 Oct;110:104271. doi: 10.1016/j.yexmp.2019.104271. Epub 2019 Jun 25.