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Nickel Induces Pyroptosis via the Nrf2/NLRP3 Pathway in Kidney of Mice

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Abstract

Nickel (Ni) is considered a toxic metal, and excessive exposure can cause kidney damage. This study was designed to explore whether nickel chloride (NiCl2) can induce cell pyroptosis and its possible mechanism. Here, we found that NiCl2 treatment could reduce the kidney index and result in kidney damage. Meanwhile, NiCl2 could obviously induce renal pyroptosis, which was characterized by an increase in IL-18, IL-1β, NLRP3, and GSDMD expression. Furthermore, NiCl2 induced pyroptosis through the Nrf2/NLRP3 pathway which featured down-regulated protein and mRNA expression levels of Nrf2 and up-regulated protein and mRNA expression levels of Caspase-1, NLRP3, and GSDMD. In summary, excessive Ni exposure can induce renal cell pyroptosis, ultimately leading to kidney tissue damage and hindering normal development, and its possible mechanism may be due to the inhibition of the Nrf2 pathway.

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Data Availability

Data are available on request due to restrictions privacy. The data presented in this study are available on request from the corresponding author. Data are not publicly available due to this paper being part of a series of studies, and disclosure of data may influence the publication of subsequent papers.

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Funding

This work was supported by Sichuan Mianyang 404 Hospital (No.: 404-220611).

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J. L., X. D., and X. J. designed and performed experiments, collected and analyzed data, and wrote the paper. S. H., Q. Y., and Z. J. performed experiments. All authors contributed discussions and interpretations. Y. Z. was responsible for the breeding of experimental animals.

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Correspondence to Xun Jian.

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Li, J., Dai, X., Hu, S. et al. Nickel Induces Pyroptosis via the Nrf2/NLRP3 Pathway in Kidney of Mice. Biol Trace Elem Res 202, 3248–3257 (2024). https://doi.org/10.1007/s12011-023-03922-7

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