Cordycepin mitigates spermatogenic and redox related expression in H2O2-exposed Leydig cells and regulates testicular oxidative apoptotic signalling in aged rats

Cordycepin (COR), from Cordyceps militaris L., (Cordycipitaceae), is a valuable agent with immense health benefits. The protective effects of COR in ageing-associated oxidative and apoptosis events in vivo and hydrogen peroxide (H 2 O 2 )-exposed spermatogenesis gene alterations in TM3 Leydig cells...

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Veröffentlicht in:Pharmaceutical biology 2022-12, Vol.60 (1), p.404-416
Hauptverfasser: Kopalli, Spandana Rajendra, Cha, Kyu-Min, Cho, Jae Youl, Kim, Si-Kwan, Koppula, Sushruta
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Cho, Jae Youl
Kim, Si-Kwan
Koppula, Sushruta
description Cordycepin (COR), from Cordyceps militaris L., (Cordycipitaceae), is a valuable agent with immense health benefits. The protective effects of COR in ageing-associated oxidative and apoptosis events in vivo and hydrogen peroxide (H 2 O 2 )-exposed spermatogenesis gene alterations in TM3 Leydig cells was investigated. Male Sprague-Dawley rats were divided into young control (YC), aged control (AC) and COR treated (COR-20) aged groups. COR-20 group received daily doses of COR (20 mg/kg) for 6 months. Cell viability and hormone levels were analysed by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] and enzyme immunoassay kits with COR treated at 1, 5, and 10 μg/mL. Oxidative enzymes, spermatogenic, and apoptotic expression in testis tissues were evaluated by Western blotting and real-time RT-PCR. COR treatment (1, 5, and 10 μg/mL) significantly (p 
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The protective effects of COR in ageing-associated oxidative and apoptosis events in vivo and hydrogen peroxide (H 2 O 2 )-exposed spermatogenesis gene alterations in TM3 Leydig cells was investigated. Male Sprague-Dawley rats were divided into young control (YC), aged control (AC) and COR treated (COR-20) aged groups. COR-20 group received daily doses of COR (20 mg/kg) for 6 months. Cell viability and hormone levels were analysed by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] and enzyme immunoassay kits with COR treated at 1, 5, and 10 μg/mL. Oxidative enzymes, spermatogenic, and apoptotic expression in testis tissues were evaluated by Western blotting and real-time RT-PCR. COR treatment (1, 5, and 10 μg/mL) significantly (p &lt; 0.05 ∼ p &lt; 0.001) inhibited the H 2 O 2 -induced decrease in the percentage of viable cells (from 63.27% to 71.25%, 85.67% and 93.97%, respectively), and reduced the malondialdehyde (MDA) content (from 4.28 to 3.98, 3.14 and 1.78 nM MDA/mg protein, respectively). Further, the decreased antioxidant enzymes (glutathione-S-transferase mu5, glutathione peroxidase 4 and peroxiredoxin 3), spermatogenesis-related factors (nectin-2 and inhibin-α) and testosterone levels in H 2 O 2 -exposed TM3 cells were significantly (p &lt; 0.05 ∼ p &lt; 0.001) ameliorated by COR. In aged rats, COR (20 mg/kg) restored the altered enzymatic and non-enzymatic antioxidative status and attenuated the apoptotic p53 and Bax/Bcl-2 expression significantly (p &lt; 0.05). COR might be developed as a potential agent against ageing-associated and oxidative stress-induced male infertility.</description><identifier>ISSN: 1388-0209</identifier><identifier>EISSN: 1744-5116</identifier><identifier>DOI: 10.1080/13880209.2022.2033275</identifier><identifier>PMID: 35175170</identifier><language>eng</language><publisher>Abingdon: Taylor &amp; Francis</publisher><subject>Aging ; Apoptosis ; BAX protein ; Bcl-2 protein ; catalase ; Cell viability ; Cordycepin ; Enzyme immunoassay ; Enzymes ; glutathione ; Glutathione peroxidase ; Glutathione transferase ; Hydrogen peroxide ; Infertility ; Inhibin ; Leydig cells ; lipid peroxidation ; Nectin ; Oxidative stress ; p53 Protein ; Peroxiredoxin ; Spermatogenesis ; spermatogenic factors ; Testosterone ; Western blotting</subject><ispartof>Pharmaceutical biology, 2022-12, Vol.60 (1), p.404-416</ispartof><rights>2022 The Author(s). 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The protective effects of COR in ageing-associated oxidative and apoptosis events in vivo and hydrogen peroxide (H 2 O 2 )-exposed spermatogenesis gene alterations in TM3 Leydig cells was investigated. Male Sprague-Dawley rats were divided into young control (YC), aged control (AC) and COR treated (COR-20) aged groups. COR-20 group received daily doses of COR (20 mg/kg) for 6 months. Cell viability and hormone levels were analysed by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] and enzyme immunoassay kits with COR treated at 1, 5, and 10 μg/mL. Oxidative enzymes, spermatogenic, and apoptotic expression in testis tissues were evaluated by Western blotting and real-time RT-PCR. 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The protective effects of COR in ageing-associated oxidative and apoptosis events in vivo and hydrogen peroxide (H 2 O 2 )-exposed spermatogenesis gene alterations in TM3 Leydig cells was investigated. Male Sprague-Dawley rats were divided into young control (YC), aged control (AC) and COR treated (COR-20) aged groups. COR-20 group received daily doses of COR (20 mg/kg) for 6 months. Cell viability and hormone levels were analysed by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] and enzyme immunoassay kits with COR treated at 1, 5, and 10 μg/mL. Oxidative enzymes, spermatogenic, and apoptotic expression in testis tissues were evaluated by Western blotting and real-time RT-PCR. COR treatment (1, 5, and 10 μg/mL) significantly (p &lt; 0.05 ∼ p &lt; 0.001) inhibited the H 2 O 2 -induced decrease in the percentage of viable cells (from 63.27% to 71.25%, 85.67% and 93.97%, respectively), and reduced the malondialdehyde (MDA) content (from 4.28 to 3.98, 3.14 and 1.78 nM MDA/mg protein, respectively). Further, the decreased antioxidant enzymes (glutathione-S-transferase mu5, glutathione peroxidase 4 and peroxiredoxin 3), spermatogenesis-related factors (nectin-2 and inhibin-α) and testosterone levels in H 2 O 2 -exposed TM3 cells were significantly (p &lt; 0.05 ∼ p &lt; 0.001) ameliorated by COR. In aged rats, COR (20 mg/kg) restored the altered enzymatic and non-enzymatic antioxidative status and attenuated the apoptotic p53 and Bax/Bcl-2 expression significantly (p &lt; 0.05). 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subjects Aging
Apoptosis
BAX protein
Bcl-2 protein
catalase
Cell viability
Cordycepin
Enzyme immunoassay
Enzymes
glutathione
Glutathione peroxidase
Glutathione transferase
Hydrogen peroxide
Infertility
Inhibin
Leydig cells
lipid peroxidation
Nectin
Oxidative stress
p53 Protein
Peroxiredoxin
Spermatogenesis
spermatogenic factors
Testosterone
Western blotting
title Cordycepin mitigates spermatogenic and redox related expression in H2O2-exposed Leydig cells and regulates testicular oxidative apoptotic signalling in aged rats
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