Edaravone reduces Aβ-induced oxidative damage in SH-SY5Y cells by activating the Nrf2/ARE signaling pathway

Life Sci. 2019 Mar 15:221:259-266. doi: 10.1016/j.lfs.2019.02.025. Epub 2019 Feb 13.

Abstract

Aims: Edaravone potentially alleviates cognitive deficits in a mouse model of Alzheimer's disease (AD). However, the mechanism of edaravone in suppressing AD progression remains unclear. We aim to investigate the mechanism of edaravone in suppressing oxidative stress-mediated AD progression in vitro.

Main methods: Human neuroblastoma SH-SY5Y cells were pretreated with different concentrations of edaravone prior to the induction by Aβ25-35. Cell viability, apoptosis, reactive oxygen species, and expression of antioxidative response elements (ARE) including Nrf2, SOD, and HO-1 were assessed.

Key findings: The results showed that apoptosis and reactive oxygen species levels significantly increased in Aβ25-35-treated cells, whereas the mRNA and protein levels of Nrf2, SOD and HO-1 decreased. The opposite changes were observed in cells that were pre-treated with edaravone, particularly at a concentration of 40 μM. Aβ25-35-treatment suppressed Nrf2 expression and nuclear translocation were rescued by Edaravone. Genetic inhibition of Nrf2 greatly decreased the protective effect of edaravone against cell apoptosis and cytotoxicity induced by Aβ25-35, accompanied by decreases in SOD and HO-1 expression.

Significance: Activation of the Nrf2/ARE signaling pathway may underlie the protective effects of edaravone against the oxidative damage associated with Alzheimer's disease.

Keywords: Alzheimer's disease; Aβ(25–35); Edaravone; Nrf2/ARE; Oxidative damage.

MeSH terms

  • Alzheimer Disease / metabolism
  • Amyloid beta-Peptides / adverse effects
  • Amyloid beta-Peptides / drug effects*
  • Animals
  • Antioxidant Response Elements / drug effects
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cognitive Dysfunction / metabolism
  • Disease Models, Animal
  • Edaravone / metabolism*
  • Humans
  • NF-E2-Related Factor 2 / drug effects
  • Neuroblastoma
  • Neuroprotective Agents
  • Oxidation-Reduction
  • Oxidative Stress / drug effects*
  • Peptide Fragments / adverse effects
  • Peptide Fragments / drug effects*
  • Reactive Oxygen Species / metabolism
  • Signal Transduction
  • Superoxide Dismutase-1 / drug effects

Substances

  • Amyloid beta-Peptides
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Neuroprotective Agents
  • Peptide Fragments
  • Reactive Oxygen Species
  • amyloid beta-protein (25-35)
  • Superoxide Dismutase-1
  • Edaravone