GC-MS metabolomics analysis of mesenchymal stem cells treated with copper oxide nanoparticles

Toxicol Mech Methods. 2016 Oct;26(8):611-619. doi: 10.1080/15376516.2016.1220654. Epub 2016 Aug 23.

Abstract

Human exposure to copper oxide (CuO) nanoparticles (NPs) is rapidly increasing and for this reason reliable toxicity test systems are urgently needed. Recently, the acute cytotoxicity of CuO NPs using the new toxicity test based on human bone marrow mesenchymal stem cells (hBMMSCs) has been evaluated. It was shown that CuO NPs are much more toxic when compared to CuO microparticles (MPs). Several studies associate CuO toxicity to a possible alteration of reactive oxygen species (ROS) system. Unluckily, the mechanism that causes the toxicity is still not clear. In this work, the polar metabolite pool of treated cells, at the corresponding IC50 value, for CuO micro and NPs has been studied by gas chromatography coupled to mass spectrometry (GC-MS) and multivariate statistical data analysis. By the same means, differences due to different treatments, on samples, were investigated. Results of discriminant analysis were considered with the aim of finding the relevant metabolites unique for each class. Serine, glyceric acid, and succinic acid were upregulated on samples treated with CuO microparticles, while glutamine was the only discriminant metabolite for the class of samples treated with nanoparticles.

Keywords: Glutamine; glutathione; glycine; multivariate statistical data analysis; reactive oxygen species.

MeSH terms

  • Adult
  • Cell Culture Techniques
  • Cells, Cultured
  • Copper / chemistry
  • Copper / toxicity*
  • Female
  • Gas Chromatography-Mass Spectrometry
  • Humans
  • Male
  • Mesenchymal Stem Cells / drug effects*
  • Mesenchymal Stem Cells / metabolism
  • Metabolome / drug effects*
  • Metabolomics
  • Microscopy, Electron, Transmission
  • Middle Aged
  • Multivariate Analysis
  • Nanoparticles / chemistry
  • Nanoparticles / toxicity*
  • Particle Size
  • Surface Properties
  • Toxicity Tests / methods*

Substances

  • Copper
  • cupric oxide