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Pulmonary Exposure to Copper Oxide Nanoparticles Leads to Neurotoxicity via Oxidative Damage and Mitochondrial Dysfunction

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Abstract

Copper oxide nanoparticles (CuONPs) are widely used in pharmaceutical, food, and textile industries. They have been shown to cause lung, liver, and kidney damage. However, whether an intratracheal instillation of CuONPs would affect the brain and its underlying mechanisms remain poorly studied. In this study, healthy C57BL/6J male mice were equally subdivided into control group, low-dose (30 μg/animal), medium-dose (50 μg/animal), and high-dose (100 μg/animal) CuONPs-treated groups. Mice were subjected to acute exposure of CuONPs via intratracheal instillation. Brain histopathology, inflammatory factors, oxidative stress markers, and mitochondrial function–related protein expression were determined. Our results demonstrated that CuONPs caused a dose-dependent brain damage in mice. Histopathological changes in the brain, elevation of inflammatory factors (Tnf, Il-6), and significant alterations in oxidative stress markers were also observed after treatment with CuONPs. Intriguingly, we did not observe infiltration of macrophage cell. Moreover, Tim23, TFAM, and MFN2 protein expression levels showed the decreasing trend after treatment with CuONPs. Taken together, these results indicate that pulmonary exposure to CuONPs induces pathological damage, inflammation, oxidative stress, and mitochondrial dysfunction in the cerebral cortex, suggesting that neurotoxicity caused by pulmonary exposure of CuONPs needs more attention from the public and relevant departments.

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Funding

This research was supported by Natural Science Foundation of Fujian Province (Grant Number: 2018J05149).

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Correspondence to Zhen Zou or Chengzhi Chen.

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This study was approved by the Institutional Animal Care and Use Committee of Chongqing Medical University,which is in accordance with “The Guide for the Care and Use of Laboratory Animals”.

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The authors declare no competing interests.

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Zhou, H., Yao, L., Jiang, X. et al. Pulmonary Exposure to Copper Oxide Nanoparticles Leads to Neurotoxicity via Oxidative Damage and Mitochondrial Dysfunction. Neurotox Res 39, 1160–1170 (2021). https://doi.org/10.1007/s12640-021-00358-6

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  • DOI: https://doi.org/10.1007/s12640-021-00358-6

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