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Zinc Deficiency Induces Inflammation and Apoptosis via Oxidative Stress in the Kidneys of Mice

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Abstract

Zinc (Zn) is an essential element that regulates not only cellular immunity but also antioxidant and anti-inflammatory agents. The present study investigated the effect of Zn deficiency on renal cell apoptosis and its mechanism. A Zn-deficient kidney model in mice was created by a Zn-deficient diet. Mice were fed diets with different Zn levels for 41 days as follows: normal-Zn group (NG, 34 mg Zn/kg), low-Zn group (LG, 2 mg Zn/kg), and high-Zn group (HG, 100 mg Zn/kg). H&E staining showed that inflammatory cells and many erythrocytes exuded in the renal tissue space of the low-Zn group, and TUNEL staining indicated massive death of kidney cells in the low-Zn group. In the low-Zn group, the levels of oxygen free radicals (ROS) were significantly increased, the antioxidants were significantly decreased, and the total antioxidant capacity was decreased. Moreover, RT–qPCR and ELISA results showed that inflammatory factors (TNF-α, IL-1β, and IL-6) were significantly increased in the low-Zn group. In addition, the levels of p-IκBα, p-NF-κB p65, p-ERK, p-JNK, and p-p38 were significantly increased in the low-Zn group, indicating that zinc deficiency activates NF-κB and MAPK signalling as well as increases its expression. RT–qPCR analysis of apoptosis-related genes, including Bcl-2 Bax, Caspa8, Caspa6, and Caspa3, demonstrated that the expression levels of proapoptotic genes in mouse kidneys were significantly increased. Importantly, the in vitro results were consistent with the in vivo results. Together, these data suggested that zinc deficiency induces renal oxidative stress to activate NF-κB and MAPK signalling, thereby inducing renal cell apoptosis.

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Data Availability

The data of this study will be made available on reasonable request.

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Authors and Affiliations

  1. College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, People’s Republic of China

    Yueqi Xu, Ang Li, Xiang Li, Xian Deng & Xue-jiao Gao

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  1. Yueqi Xu
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  2. Ang Li
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  3. Xiang Li
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  4. Xian Deng
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  5. Xue-jiao Gao
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Contributions

XG and YX conceived and designed the experiments. YX, AL, and XL carried out the experiments. YX and XD processed the data. YX and XG wrote the paper. The manuscript was read and approved by all authors.

Corresponding author

Correspondence to Xue-jiao Gao.

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All the animal experiments involved in this paper have been approved by the Animal Research Ethics Committee of Northeast Agricultural University (NAUMO-2021–0119).

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The authors declare no competing interests.

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Xu, Y., Li, A., Li, X. et al. Zinc Deficiency Induces Inflammation and Apoptosis via Oxidative Stress in the Kidneys of Mice. Biol Trace Elem Res 201, 739–750 (2023). https://doi.org/10.1007/s12011-022-03166-x

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