PUBLICATION
Triptolide-induced hepatotoxicity via apoptosis and autophagy in zebrafish
- Authors
- Huo, J., Yu, Q., Zhang, Y., Liu, K., Hsiao, C.D., Jiang, Z., Zhang, L.
- ID
- ZDB-PUB-190724-3
- Date
- 2019
- Source
- Journal of applied toxicology : JAT 39(11): 1532-1540 (Journal)
- Registered Authors
- Hsiao, Chung-Der
- Keywords
- apoptosis, autophagy, hepatotoxicity, high-content imaging, triptolide, zebrafish
- MeSH Terms
-
- Animals
- Apoptosis/drug effects*
- Autophagy/drug effects*
- Autophagy-Related Protein 5/metabolism
- Beclin-1/metabolism
- Chemical and Drug Induced Liver Injury/metabolism
- Chemical and Drug Induced Liver Injury/pathology*
- Diterpenes/toxicity*
- Dose-Response Relationship, Drug
- Embryo, Nonmammalian/drug effects
- Embryo, Nonmammalian/metabolism
- Embryo, Nonmammalian/pathology
- Embryonic Development/drug effects
- Epoxy Compounds/toxicity
- Larva/drug effects
- Larva/metabolism
- Liver/drug effects*
- Liver/metabolism
- Liver/pathology
- Phenanthrenes/toxicity*
- Zebrafish*
- Zebrafish Proteins/metabolism
- PubMed
- 31321794 Full text @ J. Appl. Toxicol.
- CTD
- 31321794
Citation
Huo, J., Yu, Q., Zhang, Y., Liu, K., Hsiao, C.D., Jiang, Z., Zhang, L. (2019) Triptolide-induced hepatotoxicity via apoptosis and autophagy in zebrafish. Journal of applied toxicology : JAT. 39(11):1532-1540.
Abstract
Previous research about the development of triptolide (TP) as a natural active compound has often focused on hepatotoxicity. Among its various mechanisms, autophagy and apoptosis are two important signaling pathways. In this study, we used zebrafish to establish a TP-induced hepatotoxicity model, and investigated the roles of autophagy and apoptosis in the progress of liver injury. Zebrafish exposed to TP showed increased mortality and malformation because of the increased drug dose and duration of exposure. Meanwhile, we found that TP induced liver injury in a time- and dose-dependent manner, which was observed as a reduction in liver area, slow yolk absorption, upregulation of transaminase and local neurosis. With the application of the high-content imaging system (HCIS) technique in liver 3D imaging in vivo, clear imaging of the zebrafish liver was achieved. The results showed a decrease in volume and location of necrosis in the liver after TP exposure. Increased expression of inflammatory cytokines genes tumor necrosis factor (Tnf)α, Il1β and Il6 were shown, particularly Tnfα. The Fas-Caspase8 signaling pathway was activated. The apoptosis-related gene Bcl-2 was increased, and Bax, Caspase9 and Caspase3 were increased. However, autophagy related genes Beclin1, Atg5, Atg3 and Lc3 were increased more significantly, and the changes of Beclin1 and Atg5 were the most severe. This study successfully established a TP-induced zebrafish hepatotoxicity model and applied the HCIS technique in a zebrafish hepatotoxicity study. The result indicated Fas might be the main target of TP-induced hepatotoxicity. Autophagy played a more important role than apoptosis and was characterized by the overexpression of Beclin1 and Atg5.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping