PUBLICATION
Isoniazid causes heart looping disorder in zebrafish embryos by the induction of oxidative stress
- Authors
- Ni, J., Wang, H., Wei, X., Shen, K., Sha, Y., Dong, Y., Shu, Y., Wan, X., Cheng, J., Wang, F., Liu, Y.
- ID
- ZDB-PUB-200403-88
- Date
- 2020
- Source
- BMC pharmacology & toxicology 21: 22 (Journal)
- Registered Authors
- Keywords
- Heart looping disorder, Isoniazid, Oxidative stress
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Antitubercular Agents/adverse effects*
- Apoptosis/drug effects
- Down-Regulation
- Embryo, Nonmammalian/abnormalities
- Embryo, Nonmammalian/drug effects
- Embryo, Nonmammalian/physiopathology
- Embryonic Development/drug effects*
- Heart Defects, Congenital/chemically induced*
- Heart Defects, Congenital/genetics
- Heart Defects, Congenital/physiopathology
- Heart Rate/drug effects
- Isoniazid/adverse effects*
- Myocytes, Cardiac/drug effects
- Myocytes, Cardiac/metabolism
- Oxidative Stress/drug effects
- Reactive Oxygen Species/metabolism
- Transcription Factors/genetics
- Zebrafish
- PubMed
- 32178728 Full text @ BMC Pharmacol Toxicol
Citation
Ni, J., Wang, H., Wei, X., Shen, K., Sha, Y., Dong, Y., Shu, Y., Wan, X., Cheng, J., Wang, F., Liu, Y. (2020) Isoniazid causes heart looping disorder in zebrafish embryos by the induction of oxidative stress. BMC pharmacology & toxicology. 21:22.
Abstract
Background The cardiotoxicity of isoniazid on zebrafish embryos and its underlying mechanism is unclear.
Methods Here, we exposed zebrafish embryos at 4 h post-fertilization to different levels of isoniazid and recorded the morphology and number of malformed and dead embryos under the microscope.
Results The high concentration of isoniazid group showed more malformed and dead embryos than the low concentration of isoniazid group and control group. The morphology of the heart and its alteration were visualized using transgenic zebrafish (cmlc2: GFP) and confirmed by in situ hybridization. The negative effects of isoniazid on the developing heart were characterized by lower heart rate and more heart looping disorders. Mechanistically, PCR showed decreased expression of heart-specific transcription factors when exposed to isoniazid. Oxidative stress was induced by isoniazid in cardiomyocytes, mediated by decreased activities of catalase and superoxide dismutase, which were rescued by scavengers of reactive oxygen species.
Conclusion In conclusion, this study demonstrated that isoniazid led to heart looping disturbance by the downregulation of cardiac-specific transcription factors and induction of cardiomyocyte apoptosis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping