PUBLICATION
Imaging the radioprotective effect of amifostine in the developing brain using an apoptosis-reporting transgenic zebrafish
- Authors
- Sun, L.W.H., Asana Marican, H.T., Beh, L.K., Shen, H.
- ID
- ZDB-PUB-231104-4
- Date
- 2023
- Source
- International Journal of Radiation Biology 100(3): 433-444 (Journal)
- Registered Authors
- Shen, Hongyuan
- Keywords
- Wnt signalling, amifostine, apoptosis, cell death, cisplatin, progenitors, radiation
- MeSH Terms
-
- Amifostine*/pharmacology
- Animals
- Animals, Genetically Modified
- Apoptosis/radiation effects
- Brain
- Radiation-Protective Agents*/pharmacology
- Zebrafish
- PubMed
- 37922446 Full text @ Int. J. Radiat. Biol.
Citation
Sun, L.W.H., Asana Marican, H.T., Beh, L.K., Shen, H. (2023) Imaging the radioprotective effect of amifostine in the developing brain using an apoptosis-reporting transgenic zebrafish. International Journal of Radiation Biology. 100(3):433-444.
Abstract
Purpose Normal tissue radioprotectants alleviate radiation-induced damages and preserve critical organ functions. Investigating their efficacy in vivo remains challenging, especially in enclosed organs like the brain. An animal model that enables direct visualization of radiation-induced apoptosis while possessing the structural complexity of a vertebrate brain facilitates these studies in a precise and effective manner.
Materials and methods We employed a secA5 transgenic zebrafish expressing secreted Annexin V fused with a yellow fluorescent protein to visualize radiation-induced apoptosis in vivo. We developed a semi-automated imaging method for standardized acquisition of apoptosis signals in batches of zebrafish larvae. Using these approaches, we studied the protective effects of amifostine (WR-2721) in the irradiated zebrafish larval brain.
Results Upon 2 Gy total-body 137Cs irradiation, increased apoptosis could be visualized at high-resolution in the secA5 brain at 2, 24, and 48 hour post irradiation (hpi). Amifostine treatment (4 mM) during irradiation reduced apoptosis significantly at 24 hpi and preserved Wnt active cells in the larval brain. When the 2 Gy irradiation was delivered in combination with cisplatin treatment (0.1 mM), the radioprotective effect of amifostine was also observed.
Conclusions Our study reveals radioprotective effect of amifostine in the developing zebrafish larval brain, and highlights the utility of secA5 transgenic zebrafish as a novel system for investigating normal tissue radioprotectants in vivo.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping