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Abstract
Tramadol is an opioid pain reliever. Its abuse causes neurotoxicity in the brain cells. In high concentration, it increases the production of NO, and decreases the mitochondrial membrane potential in the central nervous system. Cellular toxicity in brain cells leads to death, by activating caspase. In this study, we aimed to investigate of chemical characterization and suppressor effects of Juglans regia essential oil on tramadol-induced cell death. PC12, rat neuron-like cell line, was used for the best simulation. The Gas Chromatography-Mass Spectroscopy (GC/MS) indicated that α-pinene and β-pinene were the most frequently found chemical constituents in J. regia essential oil. The viability and proliferation percent of all the J. regia essential oil treatments were higher than tramadol-treated cells significantly. The cell cytotoxicity and cell death index of all the J. regia essential oil treatments were lower than tramadol-treated cells. All treatment increased mitochondrial membrane potential and decreased NO production, IL-1β, IL-6, INFγ, and TNFα release, and Caspase-3 activity. We concluded that J. regia essential oil suppressed the tramadol-induced cell death in neuron-like, PC12 cells through inhibition of NO production, mitochondrial membrane disruption, DNA fragmentation, and caspase-3 activity.