PUBLICATION
Nitazoxanide induced myocardial injury in zebrafish embryos by activating oxidative stress response
- Authors
- Gong, F., Shen, T., Zhang, J., Wang, X., Fan, G., Che, X., Xu, Z., Jia, K., Huang, Y., Li, X., Lu, H.
- ID
- ZDB-PUB-210918-28
- Date
- 2021
- Source
- Journal of Cellular and Molecular Medicine 25(20): 9740-9752 (Journal)
- Registered Authors
- Lu, Huiqiang
- Keywords
- Cardiotoxicity, Nitazoxanide, Oxidative stress, RNA-seq, Zebrafish
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Apoptosis/drug effects
- Cardiotoxicity
- Computational Biology/methods
- Disease Models, Animal
- Disease Susceptibility
- Embryo, Nonmammalian/drug effects
- Embryo, Nonmammalian/metabolism
- Gene Expression Profiling
- Gene Ontology
- Heart Injuries/etiology*
- Heart Injuries/metabolism*
- Myocytes, Cardiac/drug effects*
- Myocytes, Cardiac/metabolism*
- Nitro Compounds/adverse effects*
- Oxidative Stress/drug effects*
- Reactive Oxygen Species/metabolism
- Superoxide Dismutase/metabolism
- Thiazoles/adverse effects*
- Zebrafish
- PubMed
- 34533278 Full text @ J. Cell. Mol. Med.
Citation
Gong, F., Shen, T., Zhang, J., Wang, X., Fan, G., Che, X., Xu, Z., Jia, K., Huang, Y., Li, X., Lu, H. (2021) Nitazoxanide induced myocardial injury in zebrafish embryos by activating oxidative stress response. Journal of Cellular and Molecular Medicine. 25(20):9740-9752.
Abstract
Nitazoxanide (NTZ) is a broad-spectrum antiparasitic and antiviral drug (thiazole). However, although NTZ has been extensively used, there are no reports concerning its toxicology in vertebrates. This study used the zebrafish as a vertebrate model to evaluate the safety of NTZ and to analyse the related molecular mechanisms. The experimental results showed that zebrafish embryos exposed to NTZ had cardiac malformation and dysfunction. NTZ also significantly inhibited proliferation and promoted apoptosis in cardiomyocytes. Transcriptomic analysis used compared gene expression levels between zebrafish embryos in the NTZ treatment and the control groups identified 200 upregulated genes and 232 downregulated genes. Analysis by Kyoto encyclopaedia of genes and genomes (KEGG) and gene ontology (GO) showed that signal pathways on cardiomyocyte development were inhibited while the oxidative stress pathways were activated. Further experiments showed that NTZ increased the content of reactive oxygen species (ROS) in the hearts of zebrafish. Antioxidant gadofullerene nanoparticles (GFNPs) significantly alleviated the developmental toxicity to the heart, indicating that NTZ activated the oxidative stress response to cause embryonic cardiomyocyte injury in zebrafish. This study provides evidence that NTZ causes developmental abnormalities in the cardiovascular system of zebrafish.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping