Nitazoxanide induced myocardial injury in zebrafish embryos by activating oxidative stress response.
J Cell Mol Med
; 25(20): 9740-9752, 2021 10.
Article
en En
| MEDLINE
| ID: mdl-34533278
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Tiazoles
/
Estrés Oxidativo
/
Miocitos Cardíacos
/
Lesiones Cardíacas
/
Nitrocompuestos
Límite:
Animals
Idioma:
En
Revista:
J Cell Mol Med
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2021
Tipo del documento:
Article
País de afiliación:
China