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Crosstalk Between the Mitochondrial Dynamics and Oxidative Stress in Zinc-induced Cytotoxicity

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Abstract

Zinc is an essential trace element, which plays an important role in multiple biological activities. However, excessive exposure to zinc can cause toxic damage to living organism. Here, we investigated the relationship between oxidative stress and mitochondrial dynamics in the zinc-induced cytotoxicity. Results showed that excess exposure to zinc could significantly reduce cell viability and induce cell vacuolation in PK-15 cells. Additionally, zinc exposure caused mitochondrial dynamics disorder, manifested as mitochondrial fission, and the elevated mRNA level of Drp1 and downregulated mRNA levels of OPA1, Mfn1, and Mfn2. Meanwhile, zinc could induce oxidative damage, evidenced by the increasing levels of hydrogen peroxide, malondialdehyde, lipid peroxidation, oxidized form of nicotinamide adenine dinucleotide phosphate/nicotinamide adenine dinucleotide phosphate, oxidized glutathione/glutathione, superoxide dismutase activity, and the mRNA expression of SOD-1 and NOQ1, and decreasing levels of catalase activity, glutathione peroxidase activity, glutathione reductase activity, and the mRNA expression of CAT, and GPX1. Interestingly, N-acetyl-L-cysteine, an inhibitor for oxidative stress, could reduce the mitochondrial fission under zinc treatment. Besides, Mdivi-1, a mitochondrial fission inhibitor, could relieve oxidative stress caused by excess zinc. In general, these results suggested that mitochondrial fission and oxidative stress induced by zinc were interrelated in PK-15 cells, which is conducive to explore the new mechanism of zinc toxicity and proposes a theoretical foundation for selecting effective drugs to alleviate the toxic effects caused by zinc.

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Funding

This study was sponsored by Natural Science Foundation of Chongqing (grant number: cstc2021jcyj-msxmX1210), China, the Educational Reform Project of Chongqing Municipal Education Commission (grant number: Z213122), and the Science and Technology Research Program of Chongqing Municipal Education Commission (grant number: KJQN202003504; KJQN 202003509; KJQN202203511).

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Authors and Affiliations

  1. Laboratory of Veterinary Pharmacology, Department of Animal Science and Technology, Chongqing Three Gorges Vocational College, Chongqing, People’s Republic of China

    Qingwen Yang, Yi Zhang & Kang Yong

  2. College of Coastal Agricultural Sciences, Guangdong Ocean University, Zhanjiang, People’s Republic of China

    Junjie Yang

  3. Laboratory of Veterinary Pharmacology, Branch of Animal Husbandry and Veterinary of Heilongjiang Academy of Agricultural Sciences, Qiqihar, People’s Republic of China

    Xuesong Liu & Peng Zhong

  4. Teaching and Research Section of Pet Medicine, Pengpeng Pet Technical College, Liaoning Agricultural Technical College, Yingkou, People’s Republic of China

    Yue Li

  5. School of Pharmaceutical, Changzhou University, Changzhou, Jiangsu, People’s Republic of China

    Da Ao

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  1. Qingwen Yang
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Qingwen Yang, Junjie Yang, and Kang Yong wrote the main manuscript text, Yi Zhang, Yue Li, Da Ao, Peng Zhong and Xuesong Liu prepared figures. Qingwen Yang and Kang Yong provide the project administration. All authors reviewed the manuscript.

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Yang, Q., Yang, J., Liu, X. et al. Crosstalk Between the Mitochondrial Dynamics and Oxidative Stress in Zinc-induced Cytotoxicity. Biol Trace Elem Res 201, 4419–4428 (2023). https://doi.org/10.1007/s12011-022-03504-z

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