ZFIN ID: ZDB-PUB-200307-26
Graphene oxide nanoparticles induce hepatic dysfunction through the regulation of innate immune signaling in zebrafish (Danio rerio)
Xiong, G., Deng, Y., Liao, X., Zhang, J., Cheng, B., Cao, Z., Lu, H.
Date: 2020
Source: Nanotoxicology   14(5): 667-682 (Journal)
Registered Authors: Lu, Huiqiang
Keywords: Graphene oxide, RNA-Seq, hepatic dysfunction, inflammation, zebrafish
Microarrays: GEO:GSE145760
MeSH Terms:
  • Animals
  • Embryo, Nonmammalian/drug effects
  • Embryo, Nonmammalian/immunology
  • Embryo, Nonmammalian/metabolism
  • Gene Expression Regulation/drug effects
  • Graphite/chemistry
  • Graphite/toxicity*
  • Immunity, Innate/drug effects*
  • Larva/drug effects
  • Larva/immunology
  • Larva/metabolism
  • Lipid Metabolism/drug effects
  • Lipid Metabolism/genetics
  • Liver/drug effects*
  • Liver/immunology
  • Macrophages/cytology
  • Nanoparticles/chemistry
  • Nanoparticles/toxicity*
  • Neutrophils/cytology
  • Signal Transduction
  • Zebrafish/genetics
  • Zebrafish/immunology*
  • Zebrafish/metabolism
PubMed: 32141807 Full text @ Nanotoxicology
Graphene oxide (GO) is an increasingly important nanomaterial that exhibits great promise in the area of bionanotechnology and nanobiomedicine. However, the toxic effects of GO on the vertebrate developmental system are still poorly understood. Here, we aimed to investigate the toxic effects and molecular mechanisms of GO exposure in larval and adult zebrafish. The results showed that the major hepatotoxic phenotype induced by GO in zebrafish embryos was a significant decrease in liver area and a dose-dependent decrease in the hepatocytes. Moreover, the number of macrophages and neutrophils in zebrafish embryos were reduced but the expressions of pro-inflammatory cytokines were increased after GO treatment. High through-put RNA-Seq identified 314 differentially expressed genes (DEGs) in GO-induced zebrafish embryos including 192 up-regulated and 122 down-regulated. KEGG and GO functional analysis revealed that steroid hormone biosynthesis, lipoprotein metabolic process, and PPAR signaling pathway were significantly enriched. Most of the lipid metabolism genes were down-regulated while majority of the immune genes were up-regulated after GO treatment. Moreover, GO induced NF-κB p65 into the nucleus and increased the protein levels of NF-κB p65, JAK2, STAT3, and Bcl2 in adult zebrafish liver. In addition, pharmacological experiments showed that inhibition of ROS and blocking the MAPK signaling could rescue the hepatotoxic phenotypes induced by GO exposure. On the contrary, pharmacological activation of PPAR-α expression have increased the hepatotoxic effects in GO-induced larval and adult zebrafish. Taken together, these informations demonstrated that GO induced hepatic dysfunction mainly through the ROS and PPAR-α mediated innate immune signaling in zebrafish.