Melatonin Protects Methamphetamine-Induced Neuroinflammation Through NF-κB and Nrf2 Pathways in Glioma Cell Line

摘要: Methamphetamine (METH) is known as a toxin for neuronal and glial cells. Previous studies have found that METH-induced cell death inflammation mediated by oxidative stress. However, the exact mechanisms of inflammatory response remain unclear. Therefore, we hypothesized activation nuclear factor-κB (NF-κB) signaling, key mediator inflammation, inhibition factor erythroid 2-related factor-2 (Nrf2) regulator antioxidant response, would be significant events occurring in to rat glioma line (C6 cells). Our results show METH increased production nitric oxide (NO) up-regulated expression its main regulatory protein, inducible synthase (iNOS). also induced NF-κB increasing inhibitory κBα (IκBα) degradation translocation (p65) subunit into nucleus. Additionally, inhibited Nrf2 pathway decreasing nucleus suppressing heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase-1 (NQO-1), glutamate-cysteine ligase catalytic (γ-GCLC), resulting suppression superoxide dismutase (SOD) activity. Pretreatment with melatonin effectively promoted reversed response. Melatonin HO-1, NQO-1, γ-GCLC, SOD In addition, decreased IκBα degradation, p65 subunit, iNOS, NO production. Taken together, our indicate diminishes proinflammatory METH-stimulated C6 cells inhibiting inducing Nrf2-mediated γ-GCLC expression.