PUBLICATION

Low dose of chronic ethanol exposure in adult zebrafish induces hepatic steatosis and injury

Authors
Park, K.H., Kim, S.H.
ID
ZDB-PUB-190808-8
Date
2019
Source
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie   117: 109179 (Journal)
Registered Authors
Kim, Seok-Hyung, Park, Ki-Hoon
Keywords
Ethanol, Hepatic injury, Liver, Steatosis, Zebrafish
MeSH Terms
  • Alanine Transaminase/metabolism
  • Animals
  • Apoptosis/drug effects
  • Disease Models, Animal
  • Endoplasmic Reticulum Stress/drug effects
  • Ethanol/administration & dosage*
  • Ethanol/adverse effects*
  • Fatty Liver/chemically induced*
  • Fatty Liver/metabolism
  • Inflammation/chemically induced
  • Inflammation/metabolism
  • Lipid Metabolism/drug effects
  • Liver/drug effects*
  • Liver/metabolism
  • Liver Diseases, Alcoholic/etiology*
  • Liver Diseases, Alcoholic/metabolism
  • Male
  • Oxidative Stress/drug effects
  • Signal Transduction/drug effects
  • Zebrafish/metabolism
PubMed
31387182 Full text @ Biomed. Pharmacother.
Abstract
Chronic alcohol consumption is a major cause of chronic liver disease worldwide. Adult zebrafish have emerged as a new vertebrate model of alcoholic liver disease. In previous research, a high dose of chronic ethanol treatment induced characteristic features of steatosis and hepatic injury in adult zebrafish, yet the ethanol concentration in that study was significantly higher than the lethal dose in humans. In the current study, we examined whether a low dose of chronic ethanol exposure in adult zebrafish induced the metabolic and pathological features seen in alcoholic liver disease. We found that chronic ethanol treatment at 0.2% ethanol (v/v) concentration for 4 weeks induced a significant elevation of serum glucose and triacylglycerol in adult zebrafish. In addition, serum alanine aminotransferase activity was significantly elevated after ethanol treatment. Histological analysis revealed steatosis and hepatocyte ballooning phenotype. Gene expression analysis using quantitative real-time PCR suggested that ethanol treatment induced inflammation, apoptosis, and fibrosis. In addition, we found significant increases in gene expression involved in glucose and lipid metabolism as well as mitochondrial biogenesis and function. Importantly, expression of genes involved in oxidative and endoplasmic reticulum stress, two major stress signaling pathways underlying hepatic injury in alcoholic liver disease, were highly upregulated in the livers of adult zebrafish after chronic ethanol treatment. In conclusion, we found that 4 weeks of low dose ethanol exposure leads to typical ethanol-induced liver disease, with pathological and gene expression patterns.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping