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Selenoprotein Gene mRNA Expression Evaluation During Renal Ischemia–Reperfusion Injury in Rats and Ebselen Intervention Effects

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Abstract

Effects of selenoproteins on many renal diseases have been reported. However, their role in renal ischemia–reperfusion (I/R) injury is unclear. The present study was performed to investigate the impact of ebselen and renal I/R injury on the expression of selenoproteins. Sprague–Dawley rats were pretreated with or without ebselen (10 mg/kg) through a daily single oral administration from 3 days before renal I/R surgery. RT-qPCR (real-time quantitative PCR) was performed to determine the mRNA expression of 25 selenoprotein genes in the renal tissues. The expression levels of two selenoproteins, including GPX3 (glutathione peroxidase 3) and DIO1 (iodothyronine deiodinase 1), were evaluated by Western blot or/and IHF (immunohistofluorescence) assays. Furthermore, renal function, renal damage, oxidative stress, and apoptosis were assessed. The results showed that in renal I/R injury, the mRNA levels of 15 selenoprotein genes (GPX1, GPX3, GPX4, DIO1, DIO2, TXNRD2, TXNRD3, SEPHS2, MSRB1, SELENOF, SELENOK, SELENOO, SELENOP, SELENOS, and SELENOT) were decreased, whereas those of eight selenoprotein genes (GPX2, GPX6, DIO3, TXNRD1, SELENOH, SELENOM, SELENOV, and SELENOW) were increased. I/R also induced a reduction in the expression levels of GPX3 and DIO1 proteins. In addition, our results indicated that ebselen reversed the changes in those selenoprotein genes, excluding SELENOH, SELENOM, SELENOP, and SELENOT, in renal I/R injury and alleviated I/R-induced renal dysfunction, tissue damage, oxidative stress, and apoptosis. To our knowledge, this is the first study to investigate the changes of 25 mammalian selenoprotein genes in renal I/R injury kidneys. The present study also provided more evidence for the roles of ebselen against renal I/R injury.

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Funding

This study was sponsored by the National Natural Science Foundation of China (82160145), the Science and Technology Fund of Guizhou Health Commission ((gzwkj2021-212) and (gzwjkj2020-1–113)), and the Guizhou Science and Technology Project (QKHZC(2021)085).

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Conceptualization: Yikun Wu; data acquisition: Yikun Wu and Hua Shi; methodology: Yuangao Xu, Rao Wen, and Maodi Gong; resources: Shuxiong Xu and Hua Shi; data curation: Yikun Wu and Hua Shi; writing, review, and editing: Yikun Wu, Hua Shi, Shuxiong Xu, and Guangyi Hong; visualization: Rao Wen and Maodi Gong; supervision: Shuxiong Xu and Hua Shi; project administration and funding: Shuxiong Xu and Hua Shi. The authors declare that all data were generated in-house and that no paper mill was used.

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Correspondence to Shuxiong Xu.

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Wu, Y., Shi, H., Xu, Y. et al. Selenoprotein Gene mRNA Expression Evaluation During Renal Ischemia–Reperfusion Injury in Rats and Ebselen Intervention Effects. Biol Trace Elem Res 201, 1792–1805 (2023). https://doi.org/10.1007/s12011-022-03275-7

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