Nitazoxanide induced myocardial injury in zebrafish embryos by activating oxidative stress response
| Autor: | Tianzhu Shen, Xiaokun Li, Yong Huang, Fanghua Gong, Jiangnan Zhang, Guoqiang Fan, Kun Jia, Xiaofang Che, Huiqiang Lu, Zhaopeng Xu, Xuye Wang |
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| Rok vydání: | 2021 |
| Předmět: |
Embryo
Nonmammalian animal structures Nitazoxanide Developmental toxicity Apoptosis medicine.disease_cause Animals Genetically Modified Transcriptome parasitic diseases Gene expression medicine Animals Myocytes Cardiac KEGG Zebrafish chemistry.chemical_classification Reactive oxygen species biology Superoxide Dismutase Gene Expression Profiling Computational Biology Original Articles Cell Biology Nitro Compounds biology.organism_classification Cardiotoxicity Cell biology Disease Models Animal Oxidative Stress Thiazoles Gene Ontology Heart Injuries chemistry RNA‐seq Molecular Medicine Original Article Disease Susceptibility Reactive Oxygen Species Oxidative stress |
| Zdroj: | Journal of Cellular and Molecular Medicine |
| ISSN: | 1582-4934 1582-1838 |
| DOI: | 10.1111/jcmm.16922 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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