Dexmedetomidine affects the NOX4/Nrf2 pathway to improve renal antioxidant capacity

Abstract

Abstract This study wasintended to investigate the protective effects of dexmedetomidine (DEX) on renal injury caused by acute stress in rats and to explore the protective pathways of DEX on rat kidney from the perspective of oxidative stress.An acute restraint stress modelwas used in this study in which the rats were restrained for 3h after swimming for 15min.In this experiment, biochemical tests and histopathological sections were performed to assess renal function,followed by measurement of oxidative stress and related pathway proteins.Meanwhile,this study used NRK-52E cells for in vitro experiments and dexamethasone for stress-induced changes.The NOX4 inhibitor GLX351322 was also used to verify the inhibitory effect of DEX on NOX4.The open-field experiments confirmed that the acute stress model had been successfully established.Acute stress-induced renal injury increased NOX4 protein expression and decreased Nrf2/HO-1/NQO1 expression levels.Significant reduction in renal NOX4 expression after DEX treatment.The DEX-treated group showed significantly normalized renal biochemical results and significantly less damage observed in pathological sections compared to the acute stress group.The experimental results suggest that DEX treatment of acute stress can affect NOX4/Nrf2/HO-1/NQO1 signaling pathway and inhibit oxidative stress.Therefore,acute stress-induced kidney injury can be prevented by DEX.At the same time,DEX has potential clinical applications in stress syndromes.