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
Citation
Imran, M., Sergent, O., Tête, A., Gallais, I., Chevanne, M., Lagadic-Gossmann, D., Podechard, N. (2018) Membrane Remodeling as a Key Player of the Hepatotoxicity Induced by Co-Exposure to Benzo[a]pyrene and Ethanol of Obese Zebrafish Larvae. Biomolecules. 8(2).
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping