Prolonged exposure to carbon nanoparticles induced methylome remodeling and gene expression in zebrafish heart

J Appl Toxicol. 2019 Feb;39(2):322-332. doi: 10.1002/jat.3721. Epub 2018 Oct 5.

Abstract

Growing black carbon (BC) emission has become one of the major urgent environmental issues facing human beings. Usually, BC or BC-containing carbon nanoparticles (CNPs) were recognized as non-directly toxic components of atmospheric particulate matter. However, epidemiology studies have provided much evidence of the associations of exposure of particulate-containing carbon particles with cardiovascular diseases. There are still no related studies to support the epidemiological conclusions. Hence, in this article we exposed adult zebrafish to CNPs for 60 days, and then explored the heart location and potential adverse effects on cardiac tissues of these nanosized carbon particles. Our results first showed direct visualization of cardiac endothelial uptake and heart deposition of CNPs in zebrafish. In addition, CNPs caused significant ultrastructural alterations in myocardial tissue and induced the expression of inflammatory cytokines in a dose-dependent manner, resulting in sub-endocardial inflammation and cell apoptosis. Moreover, our data demonstrated the perturbations caused by CNPs on DNA methylation, suggesting that DNA methylome remodeling might play a critical role in CNP-induced cardiotoxicity in zebrafish heart. Therefore, this study not only proved a laboratory link between CNP exposure and cardiotoxicity in vivo, but also indicated a possible toxicity mechanism involved.

Keywords: carbon nanoparticles (CNPs); cardiotoxicity; inflammation; methylome remodeling; zebrafish.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cytokines / metabolism
  • DNA Methylation / drug effects
  • Epigenome / drug effects*
  • Epigenome / genetics
  • Female
  • Gene Expression / drug effects*
  • Heart / drug effects*
  • In Situ Nick-End Labeling
  • Male
  • Myocardium / immunology
  • Myocardium / metabolism
  • Myocardium / ultrastructure*
  • Nanoparticles / metabolism
  • Nanoparticles / toxicity*
  • Particle Size
  • Soot / metabolism
  • Soot / toxicity*
  • Tissue Distribution
  • Zebrafish*

Substances

  • Cytokines
  • Soot