Dexmedetomidine affects the NOX4/Nrf2 pathway to improve renal antioxidant capacity
Haotian Yang, Yongping Chen, Zhiqiang Wang, Yuxiang Huang, Zhigang Ma, Yue Zou, Jiaqiang Dong, Hong Zhang, Mingdong Huo, Mingzhe Lv, Xuesong Liu, Guohua Zhang, Shuang Wang, Kun Yang, Peng Zhong, Botao Jiang, Yuhong Kou, Zhifeng Chen- Pharmaceutical Science
- Pharmacology
Abstract
Objectives
The study aimed to investigate the protective effects of dexmedetomidine (DEX) on renal injury caused by acute stress in rats and explore the protective pathways of DEX on rat kidneys in terms of oxidative stress.
Methods
An acute restraint stress model was utilized, where rats were restrained for 3 hours after a 15-minute swim. Biochemical tests and histopathological sections were conducted to evaluate renal function, along with the measurement of oxidative stress and related pathway proteins.
Key findings
The open-field experiments validated the successful establishment of the acute stress model. Acute stress-induced renal injury led to increased NADPH oxidase 4 (NOX4) protein expression and decreased expression levels of nuclear transcription factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P)H: quinone oxidoreductase 1 (NQO1). Following DEX treatment, there was a significant reduction in renal NOX4 expression. The DEX-treated group exhibited normalized renal biochemical results and less damage observed in pathological sections compared to the acute stress group.
Conclusions
The findings suggest that DEX treatment during acute stress can impact the NOX4/Nrf2/HO-1/NQO1 signaling pathway and inhibit oxidative stress, thereby preventing acute stress-induced kidney injury. Additionally, DEX shows promise for clinical applications in stress syndromes.