PUBLICATION
Adult zebrafish as an in vivo drug testing model for ethanol induced acute hepatic injury
- Authors
- Park, K.H., Kim, S.H.
- ID
- ZDB-PUB-201011-4
- Date
- 2020
- Source
- Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 132: 110836 (Journal)
- Registered Authors
- Keywords
- Acute hepatic injury, Ethanol, Liver, Zebrafish
- MeSH Terms
-
- Alanine Transaminase/blood
- Alcoholism/complications
- Animals
- Disease Models, Animal*
- Ethanol/toxicity*
- Gene Expression Regulation/drug effects*
- Inflammation/drug therapy
- Inflammation/pathology
- Liver Diseases, Alcoholic/drug therapy*
- Liver Diseases, Alcoholic/genetics
- Liver Diseases, Alcoholic/physiopathology
- Niacinamide/analogs & derivatives
- Niacinamide/pharmacology
- Riboflavin/pharmacology
- Time Factors
- Zebrafish
- PubMed
- 33035832 Full text @ Biomed. Pharmacother.
Citation
Park, K.H., Kim, S.H. (2020) Adult zebrafish as an in vivo drug testing model for ethanol induced acute hepatic injury. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 132:110836.
Abstract
Chronic alcohol abuse is common and a leading cause of alcoholic liver disease (ALD). However, a safe and effective therapy for ALD is still elusive. In this study, we evaluated the utility of adult zebrafish as an in vivo model for rapid assessment of drug efficacy in ethanol-induced acute hepatic injury. We exposed adult zebrafish to 0.5 % ethanol for 24, 48, and 72 hours and measured serum alanine aminotransferase (ALT) activities. This treatment resulted in a significant increase in ALT levels at 48 and 72 h of ethanol treatment, compared to untreated control groups. Accompanying this, significant increases in mRNA expression of genes associated with inflammation was observed in the liver during ethanol exposure. To evaluate the effectiveness of drug testing using our zebrafish model for ethanol-induced acute hepatic injury, we investigated the protective function of nicotinamide riboside, a substrate for NAD+, previously shown to be protective in a rodent model of alcoholic liver disease and TES-1025, an inhibitor of α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD), that increases NAD+. We found that both nicotinamide riboside and TES-1025 treatment suppressed ethanol-induced serum ALT levels, post 48 h of ethanol exposure. In a similar manner, riboflavin supplementation also suppressed ethanol-induced serum ALT increase during ethanol exposure. Additionally, both nicotinamide riboside and riboflavin supplementation inhibited the upregulation of mRNA expression of genes associated with inflammation and de novo lipogenesis. In conclusion, we established an adult zebrafish model of ethanol-induced acute hepatic injury that will be valuable for cost-effective in vivo drug screening, which may in the future offer identification of novel therapeutics to mitigate hepatic injury, associated with excessive alcohol consumption.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping