Naringenin inhibits alcoholic injury by improving lipid metabolism and reducing apoptosis in zebrafish larvae

Lin, H., Zhou, Z., Zhong, W., Huang, P., Ma, N., Zhang, Y., Zhou, C., Lai, Y., Huang, S., An, H., Sun, X., Gao, L., Lv, Z.
Oncology reports   38(5): 2877-2884 (Journal)
Registered Authors
Ma, Ning, Zhang, Yuqing
MeSH Terms
  • Animals
  • Apoptosis/drug effects
  • Cell Cycle Proteins/genetics*
  • DNA Damage/drug effects
  • Disease Models, Animal
  • Endoplasmic Reticulum Stress/drug effects
  • Ethanol/toxicity
  • Flavanones/administration & dosage*
  • Gene Expression Regulation/drug effects
  • Humans
  • Larva/drug effects
  • Larva/genetics
  • Lipid Metabolism/drug effects
  • Liver/drug effects
  • Liver/injuries
  • Liver/pathology
  • Liver Diseases, Alcoholic/drug therapy*
  • Liver Diseases, Alcoholic/genetics
  • Liver Diseases, Alcoholic/pathology
  • Membrane Proteins/genetics*
  • Nuclear Proteins/genetics*
  • Oxidative Stress/drug effects
  • Transcription Factor CHOP/genetics*
  • Zebrafish/genetics
  • Zebrafish Proteins/genetics*
29048675 Full text @ Oncol. Rep.
Alcoholic liver disease (ALD) includes a spectrum of hepatic abnormalities that range from isolated alcoholic steatosis to steatohepatitis and cirrhosis. Naringenin, a predominant flavanone in grapefruit, increases resistance to oxidative stress and inflammation and protects against multiple organ injury in various animal models. However, the specific mechanisms responsible for protection against alcoholic injury are poorly understood. In the present study, we aimed to investigate the effect of naringenin on alcoholic events and the molecular regulatory mechanisms of naringenin in the liver and whole body of zebrafish larvae following exposure to 350 mmol/l ethanol for 32 h. Zebrafish larvae {4 days post‑fertilization (dpf); wild-type (WT) and a transgenic line with liver-specific eGFP expression [Tg(lfabp10α-eGFP)]} were used to establish an alcoholic fatty liver model in order to evaluate the effects of naringenin treatment on anti-alcoholic injury. Naringenin significantly reduced alcoholic liver morphological phenotypes and the expression of alcohol and lipid metabolism-related genes, including cyp2y3, cyp3a65, hmgcra, hmgcrb, fasn, fabp10α, fads2 and echs1, in zebrafish larvae. Naringenin also attenuated hepatic apoptosis in larvae as detected by TUNEL staining, consistent with the expression of critical biomarkers of endoplasmic reticulum stress and of DNA damage genes (chop, gadd45αa and edem1). The present study showed that naringenin inhibited alcohol-induced liver steatosis and injury in zebrafish larvae by reducing apoptosis and DNA damage and by harmonizing alcohol and lipid metabolism.
Genes / Markers
Show all Figures
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes