Cordycepin mitigates spermatogenic and redox related expression in H ₂ O ₂ -exposed Leydig cells and regulates testicular oxidative apoptotic signalling in aged rats

Abstract

Context Cordycepin (COR), from Cordyceps militaris L., (Cordycipitaceae), is a valuable agent with immense health benefits. Objective 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. Materials and methods 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. Results COR treatment (1, 5, and 10 μg/mL) significantly ( p < 0.05 ∼ p < 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 < 0.05 ∼ p < 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 < 0.05). Conclusion COR might be developed as a potential agent against ageing-associated and oxidative stress-induced male infertility.

Antioxidants (selenium and garlic) alleviated the adverse effects of tramadol on the reproductive system and oxidative stress markers in male rabbits

“…Therefore, antioxidant treatments may be efficient therapeutic choices for dealing with the burden of oxidative stress-induced male infertility 70 , 74 . In agreement with our finding, pretreatment of rats with other antioxidants [Curcumin, Gallic acid, and/or Nigella sativa oil] before tramadol administration restored such inhibition in antioxidant enzyme activities 10 , 74 , 75 . Therefore, the low number of spermatozoa and testosterone levels in tramadol-treated rabbits could be due to depletion of glutathione levels and inhibition of antioxidant enzyme activity which leads to induction of free radical levels.…”

“…In agreement with the present study, SOD, CAT, GR, GPx, and GST activities are inhibited in the livers of rats after tramadol treatment 10 . The mechanism of inhibition of antioxidant enzyme activities might be due to the interaction of tramadol or its metabolites with certain metal ions, such as selenium, that function as cofactors for antioxidant enzymes (SOD, GPx) 75 . Supporting this finding from the present study, when selenium was given to rabbits before tramadol therapy was found to increase the activities of SOD, GPx.…”

Tibetan Medicine Shi-Wei-Gan-Ning-San Alleviates Carbon Tetrachloride-Induced Chronic Liver Injury by Inhibiting TGF-β1 in Wistar Rats

“…The Crocin-treated groups were changed to DMEM medium containing Crocin after H 2 O 2 pretreatment. Drug concentrations were used as per previous studies [ 22 , 23 ]. Cell viability was detected with a 96-well plate and CCK-8 kit.…”

Social rank influences relationships between hormones and oxidative stress in a cichlid fish

“…Instead, testosterone may be helping to limit DNA damage by reducing gonadal NOX activity (especially in dominants), and although it is unclear the extent to which gonadal ROS production might influence global DNA damage, the observed negative relationship between testosterone and NOX activity has previously been observed (Juliet et al, 2004; Tam et al, 2003). Alternatively, given that high levels of oxidative stress can have inhibitory effects on gonadal androgen synthesis (Glade and Smith, 2015; Kopalli et al, 2022; Turner and Lysiak, 2008), high NOX activity in the gonads (and the associated increase in ROS production) may have supressed testosterone synthesis. This would help to explain why the negative relationship between gonadal NOX activity and testosterone levels was stronger in dominant males since the scope for reducing testosterone synthesis would be greater in dominant males.…”