Copper Nanoparticles and Copper Sulphate Induced Cytotoxicity in Hepatocyte Primary Cultures of Epinephelus coioides

PLoS One. 2016 Feb 18;11(2):e0149484. doi: 10.1371/journal.pone.0149484. eCollection 2016.

Abstract

Copper nanoparticles (Cu-NPs) were widely used in various industrial and commercial applications. The aim of this study was to analyze the cytotoxicity of Cu-NPs on primary hepatocytes of E.coioides compared with copper sulphate (CuSO4). Cultured cells were exposed to 0 or 2.4 mg Cu L-1 as CuSO4or Cu-NPs for 24-h. Results showed either form of Cu caused a dramatic loss in cell viability, more so in the CuSO4 than Cu-NPs treatment. Compared to control, either CuSO4 or Cu-NPs significantly increased reactive oxygen species(ROS) and malondialdehyde(MDA) concentration in hepatocytes by overwhelming total superoxide dismutase (T-SOD) activity, catalase(CAT) activity and glutathione(GSH) concentration. In addition, the antioxidative-related genes [SOD (Cu/Zn), SOD (Mn), CAT, GPx4] were also down-regulated. The apoptosis and necrosis percentage was significantly higher after the CuSO4 or Cu-NPs treatment than the control. The apoptosis was induced by the increased cytochrome c concentration in the cytosol and elevated caspase-3, caspase-8 and caspase-9 activities. Additionally, the apoptosis-related genes (p53, p38β and TNF-α) and protein (p53 protein) were up-regulated after the CuSO4 or Cu-NPs treatment, with CuSO4 exposure having a greater effect than Cu-NPs. In conclusion, Cu-NPs had similar types of toxic effects as CuSO4 on primary hepatocytes of E.coioides, but toxicity of CuSO4 was more severe than that of Cu-NPs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Caspases / metabolism
  • Copper / chemistry*
  • Copper / toxicity*
  • Copper Sulfate / chemistry*
  • Copper Sulfate / toxicity*
  • Cytochromes c / metabolism
  • Enzyme Activation
  • Fishes
  • Gene Expression
  • Hepatocytes / drug effects*
  • Metal Nanoparticles / chemistry*
  • Oxidative Stress / drug effects
  • Primary Cell Culture
  • Reactive Oxygen Species / metabolism

Substances

  • Reactive Oxygen Species
  • Copper
  • Cytochromes c
  • Caspases
  • Copper Sulfate

Grants and funding

The authors are grateful for the financial support of the National Key Projects of Scientific and Technical Support Programs funded by the Ministry of Science and Technology of China (No. 2011BAD13B09).