PUBLICATION
New insights into cardiotoxicity induced by chiral fluoxetine at environmental-level: Enantioselective arrhythmia in developmental zebrafish (Danio rerio)
- Authors
- Chai, T., Cui, F., Di, S., Wu, S., Zhang, Y., Wang, X.
- ID
- ZDB-PUB-201223-15
- Date
- 2020
- Source
- Environmental pollution (Barking, Essex : 1987) 270: 116182 (Journal)
- Registered Authors
- Keywords
- Arrhythmia, Biotransformation, Enantioselectivity, Fluoxetine, Norfluoxetine
- MeSH Terms
-
- Animals
- Arrhythmias, Cardiac
- Cardiotoxicity
- Fluoxetine*/toxicity
- Stereoisomerism
- Zebrafish*
- PubMed
- 33352483 Full text @ Environ. Pollut.
Citation
Chai, T., Cui, F., Di, S., Wu, S., Zhang, Y., Wang, X. (2020) New insights into cardiotoxicity induced by chiral fluoxetine at environmental-level: Enantioselective arrhythmia in developmental zebrafish (Danio rerio). Environmental pollution (Barking, Essex : 1987). 270:116182.
Abstract
Fluoxetine is frequently detected in aquatic environment, and chronic FLX exposure exhibits adverse effects on aquatic communities. Its chirality makes the adverse effects more complicated. This study aimed at the enantioselective cardiotoxicity in developmental zebrafish induced by racemic (rac-)/S-/R-fluoxetine. The accumulation profiles demonstrated that biotransformation of fluoxetine to norfluoxetine occurred during rac-fluoxetine exposure, with a higher enrichment of S-norfluoxetine than R-norfluoxetine. Heart malformations including pericardial edema, circulation abnormalities, and thrombosis were observed, and enantioselective changes also occurred. According to H&E staining and Masson's trichrome staining, the loose severity of cardiac structure and cardiac fibrosis in rac-norfluoxetine treated group was worse than that in fluoxetine treated groups. Results of toxicity-associated parameters in our homochiral enantiomers' exposure also indicated that the toxicity induced by S-fluoxetine was more severe than R-fluoxetine. Enantioselective arrhythmia in developmental zebrafish after chiral fluoxetine exposure could be caused by myocardial fibrosis, abnormal developmental processes, and the biotransformation of fluoxetine to norfluoxetine could make that worse. Our findings can be used to assess the environmental risk of the two enantiomers of fluoxetine that induce cardiotoxicity in aquatic organisms.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping