PUBLICATION

Three-dimensional integrated quantitative modeling and fluorescent imaging of doxorubicin-induced cardiotoxicity in a whole organ using a deconvolution microscope

Authors
Chen, B., Zhang, J.P.
ID
ZDB-PUB-191215-7
Date
2020
Source
Journal of Pharmacological and Toxicological Methods   101: 106662 (Journal)
Registered Authors
Keywords
3-dimensional quantification, Cardiotoxicity, Doxorubicin, Fluorescent microscope, Zebrafish
MeSH Terms
  • Animals
  • Cardiotoxicity
  • Caspase 3/metabolism
  • Doxorubicin/toxicity
  • Fluorescence
  • Heart Function Tests/drug effects
  • Heart Injuries/chemically induced
  • Heart Injuries/diagnostic imaging*
  • Heart Injuries/physiopathology*
  • Imaging, Three-Dimensional/methods*
  • Quantitative Structure-Activity Relationship
  • Reactive Oxygen Species/metabolism
  • Spatial Analysis
  • Zebrafish
PubMed
31837439 Full text @ J. Pharmacol. Toxicol. Methods
Abstract
The quantification and visualization of fluorescent staining at the whole organ level remain a challenge. Deconvolution image systems allow multi-dimensional imaging and stereo-measurement via rapid 3D reconstruction. To demonstrate this technique, we investigated doxorubicin-induced cardiotoxicity in zebrafish. Fluorogenic probe and immunofluorescence were employed to identify cardiac reactive oxygen species generation and myocardial apoptosis, respectively. We revealed the spatial distribution of fluorescent staining across the whole heart by this approach. In addition, the fluorescence intensities and fluorescence-dyed volumes in the zebrafish heart were quantified automatically. Importantly, doxorubicin treatment induced more ROS generation in the ventricle as compared to the atrium, while the levels of activated caspase-3 were much higher in the atrioventricular junction. These results would have been difficult to observe using traditional 2D images. Therefore, our deconvolution imaging strategy allows the 3D quantification and visualization of fluorescent staining at the whole organ level, and will thus support in vivo studies.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping