ZFIN ID: ZDB-PUB-090417-3
Malachite green induces cardiovascular defects in developing zebrafish (Danio rerio) embryos by blocking VEGFR-2 signaling
Jang, G.H., Park, I.S., Lee, S.H., Huh, T.L., and Lee, Y.M.
Date: 2009
Source: Biochemical and Biophysical Research Communications   382(3): 486-491 (Journal)
Registered Authors: Huh, Tae-Lin
Keywords: Malachite green, Cardiovascular defect, Zebrafish, VEGFR2 phosphorylation, Toxicity
MeSH Terms:
  • Animals
  • Apoptosis
  • Bradycardia/chemically induced
  • Cardiovascular Abnormalities/chemically induced*
  • Cardiovascular Abnormalities/enzymology
  • Cells, Cultured
  • Coloring Agents/toxicity*
  • Embryo, Nonmammalian/abnormalities
  • Embryo, Nonmammalian/drug effects
  • Embryo, Nonmammalian/enzymology
  • Endothelium, Vascular/abnormalities
  • Endothelium, Vascular/drug effects
  • Endothelium, Vascular/enzymology
  • Fungicides, Industrial/toxicity*
  • Hematopoiesis/drug effects
  • Humans
  • Neovascularization, Physiologic
  • Phosphorylation/drug effects
  • Rosaniline Dyes/toxicity*
  • Vascular Endothelial Growth Factor Receptor-2/antagonists & inhibitors*
  • Vascular Endothelial Growth Factor Receptor-2/metabolism
  • Zebrafish/abnormalities*
PubMed: 19364469 Full text @ Biochem. Biophys. Res. Commun.
Malachite green (MG) is a triphenyl methane dye used in various fields that demonstrates high toxicity to bacteria and mammalian cells. When bud stage zebrafish embryos were treated with MG at 125, 150, and 175ppb for 14h, the development of trunk including intersomitic vessels was inhibited in MG-treated flk-1-GFP transgenic embyos. MG clearly induced whole growth retardation. MG induced severe cell death in trunk intersomite region of zebrafish embryos and in human vascular endothelial cells in a dose-dependent manner. MG inhibited heart rates and cardiac looping. MG attenuated whole blood formation and inhibited vascular endothelial growth factor (VEGF)-induced receptor (R)-2 phosphorylation in vascular endothelial cells. In conclusion, MG significantly alters the cardiovascular development causing growth retardation in zebrafish through the blocking VEGFR-2 activation in early cardiovascular development. It suggests that MG may be an environmental toxic agent with the potential to induce embryonic cardiovascular defects in vertebrates.