PUBLICATION
Effects of cortisone in zebrafish (Danio rerio): Insights into gut microbiota interactions and molecular mechanisms underlying DNA damage and apoptosis
- Authors
- Tan, J., Yang, L., Ye, M., Geng, Y., Guo, Y., Zou, H., Hou, L.
- ID
- ZDB-PUB-240823-10
- Date
- 2024
- Source
- Journal of hazardous materials 478: 135576135576 (Journal)
- Registered Authors
- Keywords
- 16S rRNA, Cortisone, Molecular docking, RNA-seq, TUNEL assay
- MeSH Terms
-
- Animals
- DNA Damage*/drug effects
- Molecular Docking Simulation
- Water Pollutants, Chemical/toxicity
- Oxidative Stress/drug effects
- Caspase 3/metabolism
- Caspase 8/metabolism
- Apoptosis*/drug effects
- Cortisone*/metabolism
- Zebrafish*
- Gastrointestinal Microbiome*/drug effects
- PubMed
- 39173371 Full text @ J. Hazard. Mater.
Citation
Tan, J., Yang, L., Ye, M., Geng, Y., Guo, Y., Zou, H., Hou, L. (2024) Effects of cortisone in zebrafish (Danio rerio): Insights into gut microbiota interactions and molecular mechanisms underlying DNA damage and apoptosis. Journal of hazardous materials. 478:135576135576.
Abstract
Cortisone can enter aquatic ecosystems and pose a risk to organisms therein. However, few studies have explored the effects of cortisone on the gut microbiota of aquatic organisms. Here, we exposed zebrafish (Danio rerio) to cortisone at environmentally relevant concentrations (5.0, 50.0, or 500.0 ng L-1) for 60 days to explore its toxicological effects and their association with gut microbiota changes. The terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling assay revealed that exposure to 50 ng L-1 cortisone significantly increased the intestinal cell apoptosis rate, 8-hydroxydeoxyguanosine contents, and caspase-3 and caspase-8 activities. Moreover, the transcriptome analysis results demonstrated a notable downregulation in the expression of most differentially expressed genes associated with apoptosis pathways, as well as changes in DNA replication, oxidative stress, and drug metabolism pathways; these results indicated the occurrence of cortisone-induced stress response in zebrafish. Molecular docking analysis revealed that cortisone can bind to caspase-3 through hydrogen bonds and hydrophobic interactions but that no such interactions occur between cortisone and caspase-8. Thus, cortisone may induce oxidative DNA damage and apoptosis by activating caspase-3. Finally, the 16S rRNA sequencing results demonstrated that cortisone significantly affected microbial community structures and functions in the intestinal ecosystem. These changes may indicate gut microbiota response to cortisone-induced intestinal damage and inflammation. In conclusion, the current results clarify the mechanisms underlying intestinal response to cortisone exposure and provide a basis for evaluating the health risks of cortisone in animals.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping