PUBLICATION

Membrane Remodeling as a Key Player of the Hepatotoxicity Induced by Co-Exposure to Benzo[a]pyrene and Ethanol of Obese Zebrafish Larvae

Authors
Imran, M., Sergent, O., Tête, A., Gallais, I., Chevanne, M., Lagadic-Gossmann, D., Podechard, N.
ID
ZDB-PUB-180515-10
Date
2018
Source
Biomolecules   8(2): (Journal)
Registered Authors
Keywords
benzo[a]pyrene, co-exposure, ethanol, high-fat diet, lipid raft, liver steatosis, membrane remodeling, pravastatin, steatohepatitis, zebrafish larva
MeSH Terms
  • Animals
  • Benzo(a)pyrene/toxicity*
  • Chemical and Drug Induced Liver Injury/etiology
  • Chemical and Drug Induced Liver Injury/metabolism*
  • Chemical and Drug Induced Liver Injury/pathology
  • Ethanol/toxicity*
  • Fatty Liver/etiology
  • Fatty Liver/metabolism*
  • Fatty Liver/pathology
  • Hepatocytes/drug effects
  • Hepatocytes/pathology
  • Membrane Microdomains/drug effects*
  • Zebrafish
PubMed
29757947 Full text @ Biomolecules
Abstract
The rise in prevalence of non-alcoholic fatty liver disease (NAFLD) constitutes an important public health concern worldwide. Including obesity, numerous risk factors of NAFLD such as benzo[a]pyrene (B[a]P) and ethanol have been identified as modifying the physicochemical properties of the plasma membrane in vitro thus causing membrane remodeling-changes in membrane fluidity and lipid-raft characteristics. In this study, the possible involvement of membrane remodeling in the in vivo progression of steatosis to a steatohepatitis-like state upon co-exposure to B[a]P and ethanol was tested in obese zebrafish larvae. Larvae bearing steatosis as the result of a high-fat diet were exposed to ethanol and/or B[a]P for seven days at low concentrations coherent with human exposure in order to elicit hepatotoxicity. In this condition, the toxicant co-exposure raised global membrane order with higher lipid-raft clustering in the plasma membrane of liver cells, as evaluated by staining with the fluoroprobe di-4-ANEPPDHQ. Involvement of this membrane's remodeling was finally explored by using the lipid-raft disruptor pravastatin that counteracted the effects of toxicant co-exposure both on membrane remodeling and toxicity. Overall, it can be concluded that B[a]P/ethanol co-exposure can induce in vivo hepatotoxicity via membrane remodeling which could be considered as a good target mechanism for developing combination therapy to deal with steatohepatitis.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping