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Short-term Dietary Selenium Deficiency Induced Liver Fibrosis by Inhibiting the Akt/mTOR Signaling Pathway in Rats

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Abstract

The effects of short-term dietary selenium deficiency on the liver and protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway were evaluated. Fourteen growing rats were randomly divided into control and selenium deficiency groups and fed standard and selenium-deficient diets for 4 weeks, respectively. The serum and liver selenium concentrations were measured to evaluate the construction of animal models with selenium deficiency. Liver tissues were analyzed by transmission electron microscope, hematoxylin–eosin staining, and Masson staining to observe the ultrastructural changes, pathological changes, and severity of liver fibrosis, respectively. Besides, immunohistochemical staining (IHC) was used to analyze the effects of selenium deficiency on the expression of key proteins in the Akt/mTOR signaling pathway. The results showed that selenium concentrations in the serum and liver tissue were significantly lower in the selenium deficiency group than in the control group, and the selenium deficiency intervention could affect the morphology and structure of hepatocytes and mitochondria. Meanwhile, the liver tissue showed structural damage and fibrotic changes in the selenium deficiency group. The IHC results showed the positive staining rates of Akt, phosphorylation-modified protein kinase B (p-Akt), mTOR, and phosphorylation-modified mammalian target of the rapamycin (p-mTOR) in the liver of the selenium deficiency group which were significantly lower than that of the control group. In conclusion, short-term selenium deficiency dietary intervention could lead to liver fibrosis by inhibiting the Akt/mTOR signaling pathway.

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Acknowledgements

We thank Jian Lei and Huan Deng for their participation in the experiments of this study.

Funding

This study was supported by the National Natural Science Foundation of China (No. 81872567).

Author information

Author notes

  1. Lichun Qiao and Xue Lin contributed equally to this work.

Authors and Affiliations

  1. Department of Occupational and Environmental Health, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, 710061, Shaanxi, China

    Lichun Qiao, Xue Lin, Yan Zhao, Qingfeng Wang, Haobiao Liu, Mei You, Qian Yuan, Zhihao Yang, Wenming Bian, Jiaxin Liu, Ziwei Guo & Jing Han

  2. Global Health Institute, Health Science Center, Xi’an Jiaotong University, Xi’an, 712000, Shaanxi, China

    Lichun Qiao, Xue Lin, Yan Zhao, Qingfeng Wang, Haobiao Liu, Mei You, Qian Yuan, Zhihao Yang, Wenming Bian, Jiaxin Liu, Ziwei Guo & Jing Han

  3. Xi’an University of Science and Technology Hospital, Xi’an, 710054, Shaanxi, China

    Qingfeng Wang

  4. Shaanxi Provincial Cancer Hospital, Xi’an, 710061, Shaanxi, China

    Mei You

  5. Key Laboratory of Environment and Genes Related to Diseases, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, 710061, Shaanxi, China

    Jing Han

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  1. Lichun Qiao
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  3. Yan Zhao
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  12. Jing Han
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Contributions

Study design: Jing Han and Lichun Qiao. Animal experiments: Lichun Qiao, Xue Lin, Yan Zhao, and Haobiao Liu. Data collection: Ziwei Guo, Qingfeng Wang, and Mei You. Statistical analysis: Zhihao Yang and Qian Yuan. Figure preparation: Xue Lin, Jiaxin Liu, and Wenming Bian. Manuscript preparation: Lichun Qiao and Jing Han. All authors reviewed the manuscript.

Corresponding author

Correspondence to Jing Han.

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Ethics Approval and Consent to Participate

The study protocol was approved by the Medical Animal Research Ethics Committee of Xi’an Jiaotong University (protocol code 2018.263 and 6 March 2018 of approval).

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The authors declare no competing interests.

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Qiao, L., Lin, X., Zhao, Y. et al. Short-term Dietary Selenium Deficiency Induced Liver Fibrosis by Inhibiting the Akt/mTOR Signaling Pathway in Rats. Biol Trace Elem Res 201, 3825–3833 (2023). https://doi.org/10.1007/s12011-022-03453-7

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