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

Yazdani i, I and Ghasemnejad Berenji, M and Majdan, R (2019) Comparison of multiple doses of Cyclosporine A on germ cell apoptosis and epididymal sperm parameters after testicular ischemia/reperfusion in rats. Experimental and Molecular Pathology. pp. 1-19.

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Abstract

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° in a clockwise direction for 1 hour; 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 minutes 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<0.001). 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 longterm sperm insults were improved. Inhibition of mitochondrial permeability transition pore opening is suggested mechanism for cell protection against testicular T/D insults.

Item Type: Article
Uncontrolled Keywords: Apoptosis; Cyclosporine A; Germ cell; Mitochondrial permeability transition pore; Testicular T/D. Introduction Testicular torsion, due to spermatic cord twisting, is a traumatic inflammatory injury, which causes mitochondrial oxidative stress and germ cell apoptosis infertility results. It commonly with subfertility or affects newborns, children, and adolescent boys, totally one in 4000 males younger than 25 years, annually Ischemia in torsion which is followed by post .(Turner et al., 2004; Ghasemnejad-berenji et al., 2017) reperfusion in detorsion, is the main pathophysiological event in torsion/detorsion (T/D) injuries (Ghasemnejad‐Berenji et al., 2017). Disruption of Ca+2 homeostasis and loss of mitochondrial transmembrane potential (ΔΨm) in ischemia phase with an increase in intracellular reactive oxygen species (ROS) which arise from invaded neutrophils in reperfusion, aggravates dysregulation of respiratory chain in mitochondria and lead to predisposing of oxidative stress and cell death by mitochondrial permeability transition pore (mPTP) opening (Lysiak
Subjects: R Medicine > R Medicine (General)
Depositing User: Unnamed user with email gholipour.s@umsu.ac.ir
Date Deposited: 30 Jan 2021 07:17
Last Modified: 30 Jan 2021 07:17
URI: http://eprints.umsu.ac.ir/id/eprint/6118

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