Sevoflurane preconditioning prevents acute renal injury caused by ischemia‑reperfusion in mice via activation of the Nrf2 signaling pathway

Wang,Wen-Xi; Zhao,Zhen-Ru; Bai,Ying; Li,Ya-Xing; Gao,Xiao-Ning; Zhang,Sen; Sun,Yan-Bin

doi:10.3892/etm.2022.11232

Sevoflurane preconditioning prevents acute renal injury caused by ischemia‑reperfusion in mice via activation of the Nrf2 signaling pathway

Authors:
- Wen-Xi Wang
- Zhen-Ru Zhao
- Ying Bai
- Ya-Xing Li
- Xiao-Ning Gao
- Sen Zhang
- Yan-Bin Sun
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Affiliations: Department of Anesthesiology, Chengde Central Hospital, Chengde, Hebei 067000, P.R. China, State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, P.R. China
Published online on: February 22, 2022 https://doi.org/10.3892/etm.2022.11232
Article Number: 303
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Oxidative stress, caused by renal ischemia reperfusion (IR)/hypoperfusion, is one of the main causes of acute kidney injury (AKI). Previous studies have demonstrated that sevoflurane (SEV) protects organs from the damage caused by oxidative stress. In the present study, mice were randomly assigned to a sham operation group (Sham), IR‑vehicle group (IR+ vehicle), IR + SEV low‑dose preconditioning group and an IR + SEV high‑dose preconditioning group. The effect of SEV on nuclear factor E2‑related factor 2 (Nrf2), a key regulatory protein of the endogenous antioxidant defense system and, consequently oxidative stress, inflammation and apoptosis‑related factors, were all quantified using commercial kits or by western blotting. SEV preconditioning was demonstrated to ameliorate kidney injury as a result of decreased blood urine nitrogen and serum creatinine levels, activated Nrf2 expression in the kidney and decreased oxidative stress and inflammatory index levels an AKI mouse model. SEV preconditioning also protected injured kidney via the downregulation of caspase‑3 protein expression levels. In addition, using the Nrf2 inhibitor, Brusatol, significantly abolished the SEV preconditioning renal protective effect. Using an in vitro HK‑2 cell model of hypoxia/reoxygenation, it was also demonstrated that Nrf2 pathway activation was necessary for SEV to exert its beneficial effect for tubular cell injury caused by hypoxia/reoxygenation. These results indicated that SEV may protect against renal injury caused by IR via Nrf2 upregulation.

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