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Published on: February 15, 2021
Malachite green induces cardiovascular defects in developing zebrafish (Danio rerio) embryos by blocking VEGFR-2
Gun Hyuk Jang1, In-Sook Park, Sun Hee Lee
1Department of Natural Sciences, School of Life Sciences and Biotechnology, Kyungpook National University, Daegu 702-701, Republic of Korea.
Abstract:
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.
Insights
Malachite green (MG) dye causes zebrafish embryo growth retardation and cardiovascular defects. This toxic agent blocks vascular endothelial growth factor receptor-2 (VEGFR-2) activation, impacting early development.
Area of Science:
- Toxicology
- Developmental Biology
- Cardiovascular Science
Background:
- Malachite green (MG) is a widely used triphenyl methane dye.
- MG exhibits significant toxicity to both bacterial and mammalian cells.
Purpose of the Study:
- To investigate the effects of Malachite green on embryonic development in zebrafish.
- To determine the impact of MG on cardiovascular development and identify underlying molecular mechanisms.
Main Methods:
- Bud stage zebrafish embryos (flk-1-GFP transgenic) were exposed to varying concentrations of MG (125-175 ppb) for 14 hours.
- Assessed developmental parameters, including trunk development, intersomitic vessel formation, growth, cell death, and heart rate.
- Investigated the effect of MG on vascular endothelial growth factor receptor-2 (VEGFR-2) phosphorylation in human vascular endothelial cells.
Main Results:
- MG exposure resulted in significant growth retardation and inhibition of trunk development, including intersomitic vessels in zebrafish embryos.
- MG induced dose-dependent cell death in the trunk intersomite region of zebrafish embryos and in human vascular endothelial cells.
- MG inhibited heart rate, cardiac looping, and attenuated blood formation, while blocking vascular endothelial growth factor (VEGF)-induced VEGFR-2 phosphorylation.
Conclusions:
- Malachite green significantly disrupts cardiovascular development and causes growth retardation in zebrafish embryos.
- MG exerts its teratogenic effects by inhibiting VEGFR-2 activation during early cardiovascular development.
- MG is identified as a potential environmental toxicant capable of inducing embryonic cardiovascular defects in vertebrates.
