PUBLICATION
The combination of in silico and in vivo approaches for the investigation of disrupting effects of tris (2-chloroethyl) phosphate (TCEP) toward core receptors of zebrafish
- Authors
- Wu, Y., Su, G., Tang, S., Liu, W., Ma, Z., Zheng, X., Liu, H., Yu, H.
- ID
- ZDB-PUB-161025-1
- Date
- 2017
- Source
- Chemosphere 168: 122-130 (Journal)
- Registered Authors
- Liu, Wei
- Keywords
- Endocrine disrupting, Flame retardant, In silico, Nuclear receptors, Panoramic map, Signaling pathways
- MeSH Terms
-
- Animals
- Dose-Response Relationship, Drug
- Embryo, Nonmammalian/abnormalities
- Embryo, Nonmammalian/drug effects*
- Embryo, Nonmammalian/metabolism
- Endocrine Disruptors/analysis
- Endocrine Disruptors/metabolism
- Endocrine Disruptors/toxicity*
- Flame Retardants/analysis
- Flame Retardants/metabolism
- Flame Retardants/toxicity*
- Humans
- Molecular Docking Simulation
- Phosphines/analysis
- Phosphines/metabolism
- Phosphines/toxicity*
- Protein Binding
- Receptors, Cytoplasmic and Nuclear/genetics
- Receptors, Cytoplasmic and Nuclear/metabolism*
- Signal Transduction
- Water Pollutants, Chemical/analysis
- Water Pollutants, Chemical/metabolism
- Water Pollutants, Chemical/toxicity*
- Zebrafish*/embryology
- PubMed
- 27776230 Full text @ Chemosphere
- CTD
- 27776230
Citation
Wu, Y., Su, G., Tang, S., Liu, W., Ma, Z., Zheng, X., Liu, H., Yu, H. (2017) The combination of in silico and in vivo approaches for the investigation of disrupting effects of tris (2-chloroethyl) phosphate (TCEP) toward core receptors of zebrafish. Chemosphere. 168:122-130.
Abstract
Tris (2-chloroethyl) phosphate (TCEP), a substitute for brominated flame retardants (FRs) that have been phased out of use, is frequently detected in aqueous environments. However, previous studies on its endocrine disrupting effects have mainly focused on terrestrial mammals. Here, to comprehensively evaluate the potential adverse effects of TCEP on aquatic vertebrates, zebrafish was used as a model to examine developmental phenotypes. The underlying mechanisms of toxicity of TCEP were further explored using in silico and in vivo approaches. In vivo results demonstrated morphologic changes and mortalities of zebrafish when exposed to high concentrations (14,250 and 28,500 μg TCEP/L). In silico results showed that TCEP can bind to and interact with nuclear receptors with different patterns. The combination of in vivo and in silico analyses indicated that receptors can influence each other at the molecular level and that ER, ThR, RXR and RyR were the key receptors influencing the transcriptional pathways. Our results demonstrate that TCEP has adverse effects at relatively low concentrations by affecting key receptors and genes of vertebrates. These results exhibited the need for further studies to evaluate the potential health risks of TCEP to human infants/children due to its high concentration in Chinese rivers (up to 3700 ng/L) and potential for human exposure.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping