Protective effects of neocuproine copper chelator against oxidative damage in NSC34 cells

Mutat Res Genet Toxicol Environ Mutagen. 2018 Dec;836(Pt B):62-71. doi: 10.1016/j.mrgentox.2018.06.019. Epub 2018 Jun 25.

Abstract

In this work, we aim to provide evidence for the protective effect of a copper chelator, neocuproine (NeoCu), against the oxidative stress in NSC34 cells, which inhibits biomolecule oxidation and cell death. Results obtained with the comet assay allowed to determine the increase in oxidized purines and pyrimidines by H2O2 exposure, and their changes after the addition of NeoCu. We also observed a higher ATP7b activity in nuclei and a higher Cu concentration inside the cells, proving that the NeoCu acts directly in DNA to promote cell recovery in oxidative stress conditions, also observed in Reactive Oxygen Species (ROS) detection assay by Flow Cytometry. Based on these results, we propose that NeoCu is a promising drug for the protection of motor neuron cells during oxidative stress caused by neurodegenerative diseases in this system.

Keywords: Copper; Copper chelator; DNA protection; Genotoxicity; Neurodegeneration; Oxidative damage; Oxidative stress.

MeSH terms

  • Chelating Agents / pharmacology*
  • Copper / metabolism
  • Copper-Transporting ATPases / metabolism
  • DNA Damage*
  • Humans
  • Hydrogen Peroxide / toxicity*
  • Neuroblastoma / pathology
  • Neuroblastoma / prevention & control*
  • Oxidants / toxicity
  • Oxidative Stress / drug effects*
  • Phenanthrolines / pharmacology*
  • Protective Agents / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Tumor Cells, Cultured

Substances

  • Chelating Agents
  • Oxidants
  • Phenanthrolines
  • Protective Agents
  • Reactive Oxygen Species
  • Copper
  • neocuproine
  • Hydrogen Peroxide
  • ATP7B protein, human
  • Copper-Transporting ATPases