Neuroprotective effects of N-acetyl cysteine on primary hippocampus neurons against hydrogen peroxide-induced injury are mediated via inhibition of mitogen-activated protein kinases signal transduction and antioxidative action.

Abstract

N-acetyl cysteine (NAC) has been extensively reported to exert neuroprotective effects on the central nervous system. Oxidative stress may contribute to the underlying mechanisms causing Alzheimer's disease (AD). The effect of NAC against oxidative stress injury was investigated in a cellular model of AD in the present study and the underlying mechanisms were revealed. The neuroprotective action of NAC (1, 10, 100 and 1,000µmol/l) on a cellular model of AD [hydrogen peroxide (H2O2)‑induced (3, 30 and 300µmol/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 reactive oxygen species (ROS) levels. Furthermore, the levels of mitogen-activated protein kinases (MAPKs) signal transduction and tau protein phosphorylation were measured via western blotting. NAC (100µmol/l) protected hippocampus neurons against H2O2‑mediated toxicity, as evidenced by enhanced cell viability. Using MTT assay and light microscopy for the observation of cell death, NAC ameliorated cell viability, which was induced by H2O2 injury (P<0.05). NAC was found to mitigate the excessive production of ROS (P<0.05). Another mechanism involved in the neuroprotective 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 protective ability of NAC is hypothesized to result from inhibition of oxidative stress and downregulation of MAPK signal transduction and tau phosphorylation.