PUBLICATION
The role of hepatic antioxidant capacity and hepatobiliary transporter in liver injury induced by isopsoralen in zebrafish larvae
- Authors
- Zhang, Y., Zhang, Y., Li, J., Chen, Y., Han, L., He, Q., Chu, J., Liu, K.
- ID
- ZDB-PUB-180519-5
- Date
- 2018
- Source
- Human & Experimental Toxicology 38(1): 36-44 (Journal)
- Registered Authors
- Keywords
- Isopsoralen, antioxidant capacity, hepatobiliary transporter, hepatotoxicity, zebrafish
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Chemical and Drug Induced Liver Injury*/genetics
- Chemical and Drug Induced Liver Injury*/metabolism
- Chemical and Drug Induced Liver Injury*/pathology
- Fatty Acid-Binding Proteins/genetics
- Furocoumarins/toxicity*
- Gene Expression Regulation/drug effects
- Glutathione S-Transferase pi/genetics
- Larva
- Liver/drug effects*
- Liver/metabolism
- Liver/pathology
- Membrane Transport Proteins/genetics
- Superoxide Dismutase-1/genetics
- Zebrafish
- Zebrafish Proteins/genetics
- PubMed
- 29774767 Full text @ Hum. Exp. Toxicol.
- CTD
- 29774767
Citation
Zhang, Y., Zhang, Y., Li, J., Chen, Y., Han, L., He, Q., Chu, J., Liu, K. (2018) The role of hepatic antioxidant capacity and hepatobiliary transporter in liver injury induced by isopsoralen in zebrafish larvae. Human & Experimental Toxicology. 38(1):36-44.
Abstract
Isopsoralen is the main component of the Chinese medicine psoralen, which has antitumour activity and can be used for the treatment of osteoporosis. However, the mechanism behind its hepatotoxicity has not yet been elucidated. In this study, the hepatotoxicity of isopsoralen was investigated using zebrafish. Isopsoralen treatment groups of 25, 50 and 100 μM were established. The mortality, liver morphology changes, levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), liver histopathology and mRNA levels of liver injury-related genes in zebrafish larvae were measured. The results showed that isopsoralen resulted in the development of malformed zebrafish, dose-dependent increases in ALT and AST, decreased liver fluorescence and weakened fluorescence intensity. Histopathological examination showed that high-dose isopsoralen caused a large number of vacuolated structures in the larvae liver. The polymerase chain reaction results showed a significant decrease in the mRNA levels of genes related to antioxidant capacity ( lfabp, gstp2 and sod1) and drug transport ( mdr1, mrp1 and mrp2), indicating that isopsoralen significantly inhibited liver antioxidant capacity and drug efflux capacity in zebrafish larvae. Isopsoralen is hepatotoxic to zebrafish larvae via inhibition of drug transporter expression resulting in the accumulation of isopsoralen in the body and decreased antioxidant capacity, leading to liver injury.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping