Developmental neurotoxicity and immunotoxicity induced by graphene oxide in zebrafish embryos

Environ Toxicol. 2019 Apr;34(4):415-423. doi: 10.1002/tox.22695. Epub 2018 Dec 13.


Graphene oxide (GO) has emerged as the worldwide promising candidate for biomedical application, such as for drug delivery, bio-sensing and anti-cancer therapy. This study was focused on the zebrafish and RAW264.7 cell line as in vivo and in vitro models to assess the potential developmental neurotoxicity and immunotoxicity of GO. No obvious acute developmental toxicity was observed upon treatments with 0.01, 0.1, and 1 μg/mL GO for five consecutive days. However, decreased hatching rate, increased malformation rate, heart beat rate and hypoactivity of locomotor behavior were detected when exposed to 10 μg/mL GO. Also, RT-PCR analysis revealed that expressions of genes related to the nervous system were up-regulated. The potential risk of GO for developmental neurotoxicity may be ascribed to the high level of oxidative stress induced by high concentration of GO. Most importantly, the mRNA levels of immune response associated genes, such as interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNFα), interferon-γ (IFN-γ) were significantly increased under environmental concentration exposure. The activation of pro-inflammatory immune response was also observed in macrophage cell line. Taken together, our results demonstrated that immunotoxicity is a sensitive indicator for assessment of bio-compatibility of GO.

Keywords: Raw264.7 cells; embryotoxicity; graphene oxide; oxidative stress; zebrafish.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Dose-Response Relationship, Drug
  • Embryo, Nonmammalian / drug effects*
  • Embryo, Nonmammalian / immunology
  • Graphite / toxicity*
  • Immunity, Innate / drug effects*
  • Mice
  • Motor Activity / drug effects
  • Neurogenesis / drug effects*
  • Oxidative Stress / drug effects*
  • Oxidative Stress / immunology
  • RAW 264.7 Cells
  • Zebrafish* / embryology
  • Zebrafish* / immunology


  • graphene oxide
  • Graphite