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Overexpression of Lias Gene Alleviates Cadmium-Induced Kidney Injury in Mice Involving Multiple Effects: Metabolism, Oxidative Stress, and Inflammation

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Abstract

Oxidative stress is an important mechanism underlying toxicity induced by cadmium (Cd) exposure. However, there are significant differences of the antioxidant baseline in different populations. This means that different human has different intensity of oxidative stress in vivo after exposure to toxicants. LiasH/H mouse is a specific model which is created by genetically modifying the Lias 3′-untranslated region (3′-UTR). LiasH/H mice express high levels of LA and have high endogenous antioxidant capacity which is approximately 150% higher than wild-type C57BL/6 J mice (WT, Lias+/+). But more importantly, they have dual roles of metal chelator and antioxidant. Here, we applied this mouse model to evaluate the effect of endogenous antioxidant levels in the body on alleviating Cd-induced renal injury including Cd metabolism, oxidative stress, and inflammation. In the experiment, mice drank water containing Cd (50 mg/L), for 12 weeks. Many biomarkers of Cd metabolism, oxidative stress, inflammation, and major pathological changes in the kidney were examined. The results showed overexpression of the Lias gene decreased Cd burden in the body of mice, mitigated oxidative stress, attenuated the inflammatory response, and subsequent alleviated cadmium-induced kidney injury in mice.

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The data from the present study may be obtained from the corresponding author if the requirements are reasonable.

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Funding

This work was supported by grants 222300420516, 81703183, 222102320325, S202110472029, and YJSCX202281Y. Guangcui Xu has received research support from the Nature Science Foundation of Henan Provincial and the National Natural Science Foundation of China. Zijiang Yang and Qiyu Gao have received research support from the Scientific and Technological Research Project of Henan Provincial. Weibing Li and Jingming Gao have received research support from the Innovation and Entrepreneurship Training Project for University Students of Henan Province.

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  1. School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province, 453003, People’s Republic of China

    Guangcui Xu, Weibing Li, Yingzheng Zhao, Ting Fan, Qiyu Gao, Yongbin Wang, Fengquan Zhang, Mingjing Gao, Zhen An & Zijiang Yang

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Guangcui Xu, Yingzheng Zhao and Zijiang Yang designed this project. Guangcui Xu and Weibing Li wrote the draft. Guangcui Xu, Weibing Li, Yingzheng Zhao, Qiyu Gao and Zhen An completed the experimental work. Weibing Li,Ting Fan and Yongbin Wang performed software work and data curation. Mingjing Gao and Fengquan Zhang did animal house work. Zijiang Yang reviewed the manuscript.

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All operating protocols for mice were in following the standards set by the Animal Ethics Committee from Xinxiang Medical University (approval number: No. XYLL-2017086).

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Xu, G., Li, W., Zhao, Y. et al. Overexpression of Lias Gene Alleviates Cadmium-Induced Kidney Injury in Mice Involving Multiple Effects: Metabolism, Oxidative Stress, and Inflammation. Biol Trace Elem Res 202, 2797–2811 (2024). https://doi.org/10.1007/s12011-023-03883-x

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