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Single and Combined Effects of Short-Term Selenium Deficiency and T-2 Toxin-Induced Kidney Pathological Injury Through the MMPs/TIMPs System

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Abstract

The single and combined effects of short-term selenium (Se) deficiency and T-2 toxin-induced kidney pathological injury through the MMPs/TIMPs system were investigated. Forty-eight rats were randomly divided into control, 10 ng/g T-2 toxin, 100 ng/g T-2 toxin, Se-deficient, 10 ng/g T-2 toxin and Se deficiency combined, and 100 ng/g T-2 toxin and Se deficiency combined groups for a 4-week intervention. The kidney Se concentration was measured to evaluate the construction of animal models of Se deficiency. Kidney tissues were analyzed by hematoxylin–eosin staining, Masson staining, and transmission electron microscope to observe the pathological changes, the severity of kidney fibrosis, and ultrastructural changes, respectively. Meanwhile, quantitative polymerase chain reaction and immunohistochemical staining were used to analyze the gene and protein expression levels of matrix metallopeptidase 2/3 (MMP2/3) and tissue inhibitor of metalloproteinase 1 (TIMP1). The results showed that short-term Se deficiency and T-2 toxin exposure can cause kidney injury through tubular degeneration and even lead to kidney fibrosis. And the combination of T-2 toxin and Se deficiency had a synergistic effect on the kidney. A dose–response effect of the T-2 toxin was also observed. At the gene and protein levels, the expression of MMP2/3 in the intervention group increased, while the expression of TIMP1 decreased compared with the control group. In conclusion, short-term Se deficiency and T-2 toxin exposure might lead to injury and even the development of fibrosis in the kidneys, and combined intervention can increase the severity with a dose-dependent trend. MMP2/3 and TIMP1 likely play a significant role in the development of kidney fibrosis.

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Acknowledgements

The authors thank all study participants.

Funding

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

Author information

Author notes

  1. Ziwei Guo and Mumba mulutula Chilufya 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, China

    Ziwei Guo, Mumba mulutula Chilufya, Huan Deng, Lichun Qiao, Jiaxin Liu, Xiang Xiao, Yan Zhao, Xue Lin, Haobiao Liu, Rongqi Xiang & Jing Han

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

    Ziwei Guo, Mumba mulutula Chilufya, Huan Deng, Lichun Qiao, Jiaxin Liu, Xiang Xiao, Yan Zhao, Xue Lin, Haobiao Liu, Rongqi Xiang & Jing Han

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

    Jing Han

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  1. Ziwei Guo
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Contributions

Study design: Jing Han and Ziwei Guo. Animal experiments: Ziwei Guo, Mumba mulutula Chilufya, Huan Deng, and Lichun Qiao. Data collection: Jiaxin Liu, Xiang Xiao, and Yan Zhao. Statistical analysis: Xue Lin and Haobiao Liu. Figure preparation: Mumba mulutula Chilufya, Xue Lin, and Rongqi Xiang. Manuscript preparation: Ziwei Guo and Jing Han. All authors reviewed the manuscript.

Corresponding author

Correspondence to Jing Han.

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The authors declare no competing interests.

Ethics Approval

The animal 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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Guo, Z., Chilufya, M.m., Deng, H. et al. Single and Combined Effects of Short-Term Selenium Deficiency and T-2 Toxin-Induced Kidney Pathological Injury Through the MMPs/TIMPs System. Biol Trace Elem Res 201, 4850–4860 (2023). https://doi.org/10.1007/s12011-023-03566-7

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