PUBLICATION

Acute Exposure to Tris(1,3-dichloro-2-propyl) Phosphate (TDCIPP) Causes Hepatic Inflammation and Leads to Hepatotoxicity in Zebrafish

Authors
Liu, C., Su, G., Giesy, J.P., Letcher, R.J., Li, G., Agrawal, I., Li, J., Yu, L., Wang, J., Gong, Z.
ID
ZDB-PUB-160109-9
Date
2016
Source
Scientific Reports   6: 19045 (Journal)
Registered Authors
Gong, Zhiyuan
Keywords
none
MeSH Terms
  • Animals
  • Chemical and Drug Induced Liver Injury/genetics*
  • Chemical and Drug Induced Liver Injury/metabolism
  • Chemical and Drug Induced Liver Injury/pathology
  • Embryo, Nonmammalian
  • Endoplasmic Reticulum Stress/drug effects
  • Flame Retardants/toxicity*
  • Gene Expression Regulation, Developmental
  • Genes, Reporter
  • Inflammation
  • Larva/drug effects
  • Larva/growth & development
  • Larva/metabolism
  • Liver/drug effects*
  • Liver/growth & development
  • Liver/metabolism
  • Luminescent Proteins/genetics
  • Luminescent Proteins/metabolism
  • Male
  • NAD(P)H Dehydrogenase (Quinone)/genetics
  • NAD(P)H Dehydrogenase (Quinone)/metabolism
  • Neutrophil Infiltration/drug effects
  • Neutrophils/drug effects
  • Neutrophils/metabolism
  • Neutrophils/pathology
  • Organophosphorus Compounds/toxicity*
  • Protein Serine-Threonine Kinases/genetics
  • Protein Serine-Threonine Kinases/metabolism
  • Toll-Like Receptors/genetics
  • Toll-Like Receptors/metabolism
  • Water Pollutants, Chemical/toxicity*
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed
26743178 Full text @ Sci. Rep.
CTD
26743178
Abstract
Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) has been frequently detected in environmental media and has adverse health effect on wildlife and humans. It has been implicated to have hepatotoxicity, but its molecular mechanisms remain unclear. In the present study, adult male zebrafish were exposed to TDCIPP and global hepatic gene expression was examined by RNA-Seq and RT-qPCR in order to understand the molecular mechanisms of TDCIPP-induced hepatotoxicity. Our results indicated that TDCIPP exposure significantly up-regulated the expression of genes involved in endoplasmic reticulum stress and Toll-like receptor (TLR) pathway, implying an inflammatory response, which was supported by up-regulation of inflammation-related biomaker genes. Hepatic inflammation was further confirmed by histological observation of increase of infiltrated neutrophils and direct observation of liver recruitment of neutrophils labeled with Ds-Red fluorescent protein of Tg(lysC:DsRed) zebrafish upon TDCIPP exposure. To further characterize the hepatotoxicity of TDCIPP, the expression of hepatotoxicity biomarker genes, liver histopathology and morphology were examined. The exposure to TDCIPP significantly up-regulated the expression of several biomarker genes for hepatotoxicity (gck, gsr and nqo1) and caused hepatic vacuolization and apoptosis as well as increase of the liver size. Collectively, our results suggest that exposure to TDCIPP induces hepatic inflammation and leads to hepatotoxicity in zebrafish.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping