Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Dexmedetomidine inhibits oxidative stress in sepsis-induced acute kidney injury in rats by regulating GSK-3 β/Nrf2/ARE axis

Yan Jing, Li Yao, Weicui Du, Jia Liu, Rongrong Yang, Wanchang Zhou, Xiaolin Xu, Jingjing Cao, Lichao Zhang, Chengjing Si

Department of Nephrology, The Fourth Affiliated Hospital of Gansu University of Chinese Medicine, Lanzhou 730060, Gansu Province, China;

For correspondence:- Chengjing Si Email: kpcpu5@163.com

Accepted: 28 June 2021 Published: 29 July 2021

Citation: Jing Y, Yao L, Du W, Liu J, Yang R, Zhou W, et al. Dexmedetomidine inhibits oxidative stress in sepsis-induced acute kidney injury in rats by regulating GSK-3 β/Nrf2/ARE axis. Trop J Pharm Res 2021; 20(7):1381-1386 doi: 10.4314/tjpr.v20i7.9

© 2021 The authors.
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Abstract

Purpose: To determine the effect of dexmedetomidine on sepsis-mediated acute kidney injury (SAKI) in rats.

Methods: Twenty-four SD rats were randomly divided into blank untreated control group, model group given lipopolysaccharide at a dose of 10 mg/kg, dexmedetomidine (Dex) group, and glycogen synthase kinase-3 beta (GSK-3β) inhibitor group given sb216763. In addition, Dex and inhibitor groups received the same dose of lipopolysaccharide as model group. There were 10 rats in each group. Pathological changes in kidney tissue, and the levels of related oxidative stress indices were determined.

Results: Compared with the model group, granular degeneration of renal tubular epithelial cells was significantly reduced in Dex group, and the population of exfoliated cells decreased (p < 0.05). The levels of malondialdehyde (MDA) and reactive oxygen species (ROS) in dexmedetomidine and GSK-3β inhibitor groups were significantly reduced, while superoxide dismutase (SOD), glutathione (GSH) and catalase (CAT) activities were markedly raised, relative to model group (p < 0.05). Protein levels of p-GSK-3β and Nrf2 markedly were raised in dexmedetomidine and GSK-3β inhibitor groups (p < 0.01). After intervention with Dex and GSK-3β inhibitor, there were marked upregulations in mRNA and protein expression levels of heme oxygenase-1 (HO-1), when compared with model group (p < 0.05).

Conclusion: Dexmedetomidine ameliorates SAKI injury in rats via suppression of oxidative stress. Its mechanism of action may be related to the regulation of GSK-3β/Nrf2/ARE signaling pathway. This finding may be a novel approach to the clinical management of SAKI.

Keywords: Dexmedetomidine, GSK-3?/Nrf2/ARE signal pathway, Sepsis, AKI, Oxidative stress