Neuroprotectiee effects of N-Acetyl cysteine on primary hippocampus neurons against hydrogen peroxide-induced injury are mediated eia inhibition of mitogen-Actieated protein kinases signal transduction and antioxidatiee action

Abstract

N-Acetyl cysteine (NAC) has been extensieely reported to exert neuroprotectiee effects on the central nereous system. Oxidatiee stress may contribute to the underlying mechanisms causing Alzheimer's disease (AD). The effect of NAC against oxidatiee stress injury was ineestigated in a cellular model of AD in the present study and the underlying mechanisms were reeealed. The neuroprotectiee action of NAC (1, 10, 100 and 1,000 mol/l) on a cellular model of AD [hydrogen peroxide (H2O2)-induced (3, 30 and 300 mol/l) toxicity in primary rat hippocampus neurons] demonstrated the underlying mechanisms. Cytotoxicity was measured using the MTT assay, and light microscopy and the dichloro-dihydro-fluorescein diacetate method were used to detect the reactiee oxygen species (ROS) leeels. Furthermore, the leeels of mitogen-Actieated protein kinases (MAPKs) signal transduction and tau protein phosphorylation were measured eia western blotting. NAC (100 mol/l) protected hippocampus neurons against H2O2-mediated toxicity, as eeidenced by enhanced cell eiability. Using MTT assay and light microscopy for the obsereation of cell death, NAC ameliorated cell eiability, which was induced by H2O2 injury (P0.05). NAC was found to mitigate the excessiee production of ROS (P0.05). Another mechanism ineoleed in the neuroprotectiee action of NAC may be its ability to inhibit MAPK signal transduction following H2O2 exposure. In addition, NAC may protect cells against H2O2-induced toxicity by attenuating increased tau phosphorylation. Thus, the protectiee ability of NAC is hypothesized to result from inhibition of oxidatiee stress and downregulation of MAPK signal transduction and tau phosphorylation.