High-Dose Dexmedetomidine Promotes Apoptosis in Fetal Rat Hippocampal Neurons

Abstract

Objective Dexmedetomidine (DEX) is a potent a2-adrenoceptor agonist that has sedative, analgesic, and anxiolytic effects. Its primary clinical use is as an adjunct to general anesthesia to reduce anesthetic doses, provide analgesia and sedation in the preoperative and postoperative periods, it also used in intensive care units (ICUs). However, high concentrations of DEX may have toxic effects on neurons and cause neuronal apoptosis. This study aimed to evaluate the potential proapoptotic effects of DEX on fetal rat hippocampal neurons. Methods Primary hippocampal were cultured in vitro for 8 days and incubated with different DEX concentrations for 3 h. Cell viability was measured using cell counting kit-8 assays. Cell apoptosis was evaluated using flow cytometry. The expression of apoptosis-related proteins, such as cleaved caspase-3, caspase-9, Cyt-c, Bax, and Bcl-2, was measured by Western blotting. The mitochondrial ATP levels, Δψm, and ROS analyzed were conducted. Results High concentrations of DEX (≥100 μM) significantly reduced cell viability, induced neuronal apoptosis, upregulated the protein expression of cleaved caspase 3, Bax, cleaved caspase 9, and Cyt-c. DEX also considerably promoted the release of ROS. However, DEX (≥100 μM) downregulated the protein expression of Bcl-2, decreased the mitochondrial membrane potential (MTP), and reduced ATP synthesis. Conclusion High concentrations of dexmedetomidine produced toxic effects on neurons and caused neuronal apoptosis.