Remifentanil Suppresses Oxidative Stress and Inflammation Induced by Glutamate via Activation of PPARγ/HO-1 Signaling Pathway in Hippocampal Neuronal Cells

Abstract

Excitotoxicity caused by glutamate severely damages the central nervous system, contributing to the progress of neurodegenerative diseases. Remifentanil is an ultra-short acting synthetic α-opioid receptor agonist and it protects the body against oxidative stress. Oxidative stress is a causative factor for neuronal cell death, contributing to the pathogenesis of neurological diseases. More importantly, remifentanil has been confirmed to have neuroprotective effects on cerebral ischemia. Hence, the aim of the present study was to investigate the molecular mechanism underlying the effect of remifentanil on glutamate (Glu)-induced oxidative stress and inflammation in hippocampal cells. In present study, the cell viability was detected via CCk-8 assay. The cell apoptosis was evaluated by tunel assay. Western blot was performed for measurement of protein expression level. Generation of ROS level was detected by the ROS Activity Assay Kit (KA3842, Abnova) and DCF-DA staining method. MDA and SOD levels were detected by corresponding kits. The results from the present study suggested that remifentanil enhanced cell viability, reduced cell apoptosis rate and prevented oxidative stress in glutamate-induced HT22 cells. The PPARγ/HO-1 pathway was activated by remifentanil. After inhibition of PPARγ/HO-1 pathway, the anti-apoptosis and anti-oxidative stress effects of remifentanil were abolished. In conclusion, remifentanil has anti-apoptosis and anti-oxidative stress effects on glutamate-induced HT22 Cells via PPARγ/HO-1 pathway. Hence, remifentanil is a promising agent for attenuation of cytotoxicity induced by glutamate, providing a new strategy for treatment of excitotoxicity caused by glutamate in the central nervous system.