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Selenium Alleviates Ammonia-Induced Splenic Cell Apoptosis and Inflammation by Regulating the Interleukin Family/Death Receptor Axis and Nrf2 Signaling Pathway

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Abstract

Ammonia (NH3) is a harmful gas in livestock houses. So far, many researchers have demonstrated that NH3 is detrimental to animal and human organs. Selenium (Se) is one of the essential trace elements in the body and has a good antioxidant effect. However, there was little conclusive evidence that Se alleviated NH3 poisoning. To investigate the toxic mechanism of NH3 on pig spleen and the antagonistic effect of L-selenomethionine, a porcine NH3-poisoning model and an L-selenomethionine intervention model were established in this study. Our results showed that NH3 exposure increased the apoptosis rate, while L-selenomethionine supplementation alleviated the process of excessive apoptosis. Immunofluorescence staining, real-time quantitative polymerase chain reaction (qRT-PCR), and western blot results confirmed that exposure to NH3 changed the expression levels of interleukin family factors, apoptosis, death receptor, and oxidative stress factors. Our study further confirmed that excessive NH3 induced inflammatory response and mediated necroptosis leading to cell apoptosis by activating the Nrf2 signaling pathway. Excessive NH3 could mediate spleen injury through oxidative stress-induced mitochondrial dynamics disorder. L-Selenomethionine could alleviate inflammation and abnormal apoptosis by inhibiting the IL-17/TNF-α/FADD axis. Our study would pave the way for comparative medicine and environmental toxicology.

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Data Availability

All original data (including the raw sequencing files) used in the current manuscript could be available to access from the corresponding author (jbao@neau.edu.cn). You can find supplementary files related to this article online.

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Acknowledgements

Thanks are given to the Animal Welfare Team of Northeast Agricultural University for supporting this study. All authors thank Lian Chuan-Biotechnology Co., Ltd. (Hangzhou, China) for their help in transcriptome sequencing.

Funding

This study was supported by the China Agriculture Research System of MOF and MARA (Project No. CARS-35-05B).

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Authors and Affiliations

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

    Jing Wang, Yutao Li, Jianxing Wang & Jun Bao

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

    Yulai Wang, Honggui Liu & Jun Bao

  3. Key Laboratory of Swine Facilities Engineering, Ministry of Agriculture and Rural Affairs, Harbin, People’s Republic of China

    Jun Bao

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  1. Jing Wang
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  4. Yulai Wang
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  5. Honggui Liu
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Contributions

Jun Bao, Honggui Liu, and Jing Wang: conceived and designed the current experiments plans. Jing Wang: wrote the manuscript and completed the experiments. Yutao Li: analyzed these data. Jianxing Wang and Yulai Wang: provided help during animal breeding. Jun Bao and Honggui Liu: revised the whole manuscript.

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Correspondence to Jun Bao.

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The Animal Ethics Committee approved all procedures in this experiment of Northeast Agricultural University (No. SRM-06).

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Wang, J., Li, Y., Wang, J. et al. Selenium Alleviates Ammonia-Induced Splenic Cell Apoptosis and Inflammation by Regulating the Interleukin Family/Death Receptor Axis and Nrf2 Signaling Pathway. Biol Trace Elem Res 201, 1748–1760 (2023). https://doi.org/10.1007/s12011-022-03279-3

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