Citicoline protects against lead-induced oxidative injury in neuronal PC12 cells

Biochem Cell Biol. 2019 Dec;97(6):715-721. doi: 10.1139/bcb-2018-0218. Epub 2019 Mar 29.


Lead is a major environmental pollutant that causes serious adverse effects on biological systems and cells. In this study, we examined the effect of citicoline on lead-induced apoptosis in PC12 cells. The PC12 cells were pre-treated with citicoline and then exposed to lead for 48 h. The effect of citicoline on cell survival was examined by MTT assay. In addition, levels of lipid peroxidation (LPO), total thiol groups, total antioxidant power (TAP), catalase (CAT), superoxide dismutase (SOD), and reduced glutathione (GSH) were evaluated. The levels of Bax, Bcl-2, and caspase-3 were also measured, by Western blot analysis. Citicoline significantly increased the cell viability of PC12 cells exposed to lead. Treatment of PC12 cells with lead increased LPO levels, and citicoline effectively decreased LPO. Levels of total thiol groups and TAP, CAT, SOD, and GSH were significantly increased in citicoline-treated PC12 cells compared with the lead-treated group. Citicoline pretreatment significantly reduced Bax expression, and increased the level of Bcl-2 expression. Citicoline also reduced caspase-3 activation in PC12 cells compared with the lead-treated group. Our findings indicate that citicoline exerts a neuroprotective effect against lead-induced injury in PC12 cells through mitigation of oxidative stress and, at least in part, through suppression of the mitochondria-mediated apoptotic pathway.

Keywords: PC12 cells; apoptose; apoptosis; cellules PC12; citicoline; lead toxicity; oxidative stress; stress oxydant; toxicité du plomb.

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Apoptosis / drug effects
  • Cell Survival / drug effects
  • Cytidine Diphosphate Choline / pharmacology*
  • Lead / toxicity*
  • Lipid Peroxidation / drug effects
  • Mitochondria / drug effects
  • Oxidative Stress / drug effects
  • PC12 Cells
  • Protective Agents / pharmacology*
  • Rats


  • Antioxidants
  • Protective Agents
  • Lead
  • Cytidine Diphosphate Choline