PUBLICATION
Triclosan-induced liver injury in zebrafish (Danio rerio) via regulating MAPK/p53 signaling pathway
- Authors
- Liu, M., Ai, W., Sun, L., Fang, F., Wang, X., Chen, S., Wang, H.
- ID
- ZDB-PUB-190507-14
- Date
- 2019
- Source
- Comparative biochemistry and physiology. Toxicology & pharmacology : CBP 222: 108-117 (Journal)
- Registered Authors
- Keywords
- Bax, Bcl-2, Hepatocyte apoptosis, Liver injury, MAPK/p53 signaling pathway, Triclosan exposure
- MeSH Terms
-
- Animals
- Biomarkers
- Chemical and Drug Induced Liver Injury/metabolism
- Chemical and Drug Induced Liver Injury/pathology
- Chemical and Drug Induced Liver Injury/veterinary*
- Fish Diseases/chemically induced
- Gene Expression Regulation/drug effects*
- Hepatocytes/drug effects
- Hepatocytes/metabolism
- Larva/drug effects
- Mitogen-Activated Protein Kinase Kinases/genetics
- Mitogen-Activated Protein Kinase Kinases/metabolism*
- Triclosan/toxicity*
- Tumor Suppressor Protein p53/genetics
- Tumor Suppressor Protein p53/metabolism*
- Zebrafish*
- PubMed
- 31048017 Full text @ Comp. Biochem. Physiol. C Toxicol. Pharmacol.
Citation
Liu, M., Ai, W., Sun, L., Fang, F., Wang, X., Chen, S., Wang, H. (2019) Triclosan-induced liver injury in zebrafish (Danio rerio) via regulating MAPK/p53 signaling pathway. Comparative biochemistry and physiology. Toxicology & pharmacology : CBP. 222:108-117.
Abstract
Long-term exposure of triclosan (TCS), an important antimicrobial agent, can lead to deleterious effects on liver growth and development. However, the related mechanisms on TCS-induced hepatocyte injury remain unclear. Herein, we found that after long-time TCS exposure to adult zebrafish (Danio rerio) from 6 hpf (hours post-fertilization) to 90 dpf (days post-fertilization), the body weight and hepatic weight were significantly increased in concomitant with a large amount of lipid droplet accumulation in liver. Also, TCS exposure resulted in occurrence of oxidative stress by increasing the concentrations of malondialdehyde and reducing the activity of superoxide dismutase both in zebrafish larvae (120 hpf) and adult liver. By H&E staining, we observed a series of abnormal phenomena such as severely hepatocellular atrophy and necrosis, as well as prominently increased hepatic plate gap in TCS-exposure treatment groups. Through AO staining, TCS induced obvious apoptosis in larval heart and liver; through TUNEL assay, a concentration-dependent apoptosis was found to mainly occur in adult liver and its surrounding tissues. The mRNA and protein expression of anti-apoptotic protein Bcl-2 decreased, while that of pro-apoptosis protein Bax significantly increased, identifying that liver injury was closely related to hepatocyte apoptosis. The significant up-regulation of MAPK and p53 at both mRNA and protein levels proved that TCS-induced hepatocyte apoptosis was closely related to activating the MAPK/p53 signaling pathway. These results strongly suggest that long-term TCS-exposure may pose a great injury to zebrafish liver development by means of activating MAPK/p53 apoptotic signaling pathway, also lay theoretical foundation for further assessing TCS-induced ecological healthy risk.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping