Dexmedetomidine ameliorates acute stress-induced kidney injury by attenuating oxidative stress and apoptosis through inhibition of the ROS/JNK signaling pathway

Abstract

Acute stress induces tissue damage through excessive oxidative stress. Dexmedetomidine (DEX) reportedly has an antioxidant effect. However, protective roles and related potential molecular mechanisms of DEX against kidney injury induced by acute stress are unknown. Herein, rats were forced to swim 15 min followed by restraint stress for 3 h with/without DEX (30 μg/kg). Successful model establishment was validated by an open-field test. Assessment of renal function (creatinine, urea nitrogen), histopathology, oxidative stress (malondialdehyde, glutathione, and superoxide dismutase), and apoptosis (transferase-mediated dUTP nick end labeling) was performed. Localization of apoptosis was determined by immunohistochemistry of cleaved caspase 3 protein. In addition, key proteins of the death receptor-mediated pathway, mitochondrial pathway, endoplasmic reticulum stress (ERS) pathway, and ROS/JNK signaling pathway were measured by Western blot. We found that DEX significantly improved renal dysfunction, ameliorated kidney injury, reduced oxidative stress, and alleviated apoptosis. DEX also inhibited the release of norepinephrine (NE), decreased the production of reactive oxygen species (ROS), and inhibited JNK phosphorylation. Additionally, DEX downregulated the expression of Bax, cytochrome C, cleaved caspase 9, and cleaved caspase 3 proteins in mitochondria-dependent pathways. In summary, DEX protects against acute stress-induced kidney injury in rats by reducing oxidative stress and apoptosis via inhibition of the ROS/JNK pathway.