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Antagonistic effect of selenium on programmed necrosis of testicular Leydig cells caused by cadmium through endoplasmic reticulum stress in chicken

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Abstract

Cadmium (Cd) is a widely distributed environmental contaminant that is highly toxic to animals and humans. However, detailed reports on Cd-induced programmed necrosis have not been seen in chicken testicular Leydig cells. Selenium (Se) is a trace element in the human body that has cytoprotective effects in a variety of pathological damages caused by heavy metals. This study investigated the potential mechanisms of Cd-induced programmed cell necrosis and the antagonistic effect of Se on Cd toxicity. Chicken testis Leydig cells were divided into six groups, namely, control, Se (5 µmol/L Na2SeO3), Cd (20 µmol/L CdCl2), Se + Cd (5 µmol/L Na2SeO3 and 20 µmol/L CdCl2), 4-phenylbutyric acid (4-PBA) + Cd (10 mmol/L 4-phenylbutyric acid and 20 µmol/L CdCl2), and Necrostatin-1 (Nec-1) + Cd (60 µmol/L Necrostatin-1 and 20 µmol/L CdCl2). The results showed that Cd exposure decreased the activity of CAT, GSH-Px, and SOD and the concentration of GSH, and increased the concentration of MDA and the content of ROS. Relative mRNA and protein expression of GRP78, PERK, ATF6, IRE1, CHOP, and JNK increased in the Cd group, and mRNA and protein expression of TNF-α, TNFR1, RIP1, RIP3, MLKL, and PARP1 significantly increased in the Cd group, while Caspase-8 mRNA and protein expression significantly decreased. The abnormal expression of endoplasmic reticulum stress-related proteins was significantly reduced by 4-PBA pretreatment; the increased expression of TNF-α, TNFR1, RIP1, RIP3, MLKL, and PARP1 caused by Cd toxicity was alleviated; and the expression of caspase-8 was upregulated. Conversely, the increased mRNA and protein expression of endoplasmic reticulum stress marker genes (GRP78, ATF6, PERK, IRE1, CHOP, JNK) caused by Cd was not affected after pretreatment with Nec-1. We also found that these Cd-induced changes were significantly attenuated in the Se + Cd group. We clarified that Cd can cause programmed necrosis of chicken testicular Leydig cells through endoplasmic reticulum stress, and Se can antagonize Cd-induced programmed necrosis of chicken testicular Leydig cells.

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Data availability

All data in the current study are available from the corresponding author on reasonable request.

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Funding

This research was supported by the Heilongjiang Province on Natural Fund Project of China (Grant No. LH2019C026).

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Authors and Affiliations

  1. College of Animal Science and Technology, Northeast Agricultural University, Harbin, 150030, People’s Republic of China

    Lulu Hou, Size Wang, Yueyue Wang, Min Wang, Zilin Cui & He Huang

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  1. Lulu Hou
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  2. Size Wang
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  3. Yueyue Wang
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  4. Min Wang
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  6. He Huang
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Contributions

Lulu Hou designed and conducted the experiments and wrote the article. Size Wang, Yueyue Wang, and Min Wang conducted the experiments and wrote the article. Zilin Cui contributed to the conduction of the experiments. He Huang designed the experiments and wrote and revised the article.

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Correspondence to He Huang.

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All procedures used in this experiment were approved by the Northeast Agricultural University’s Institutional Animal Care and Use Committee under the approved protocol number SRM-06.

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All authors read and approved the final manuscript. They agreed with the publication and consented to submit. They obtained consent from the responsible authorities at the Northeast Agricultural University.

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Hou, L., Wang, S., Wang, Y. et al. Antagonistic effect of selenium on programmed necrosis of testicular Leydig cells caused by cadmium through endoplasmic reticulum stress in chicken. Environ Sci Pollut Res 30, 112517–112535 (2023). https://doi.org/10.1007/s11356-023-29803-z

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