PUBLICATION
α-asarone induces cardiac defects and QT prolongation through mitochondrial apoptosis pathway in zebrafish
- Authors
- Shang, X., Ji, X., Dang, J., Wang, L., Sun, C., Liu, K., Sik, A., Jin, M.
- ID
- ZDB-PUB-200209-6
- Date
- 2020
- Source
- Toxicology letters 324: 1-11 (Journal)
- Registered Authors
- Keywords
- QT duration, T-wave, apoptosis, cardiotoxicity, zebrafish
- MeSH Terms
-
- Abnormalities, Drug-Induced/etiology*
- Animals
- Anisoles/toxicity*
- Apoptosis/drug effects*
- Cardiotoxicity/etiology
- Electrocardiography/drug effects*
- Embryo, Nonmammalian/drug effects
- Heart Defects, Congenital/chemically induced*
- Mitochondria, Heart/drug effects*
- Mitochondria, Heart/pathology
- Zebrafish
- PubMed
- 32035120 Full text @ Toxicol. Lett.
- CTD
- 32035120
Citation
Shang, X., Ji, X., Dang, J., Wang, L., Sun, C., Liu, K., Sik, A., Jin, M. (2020) α-asarone induces cardiac defects and QT prolongation through mitochondrial apoptosis pathway in zebrafish. Toxicology letters. 324:1-11.
Abstract
α-asarone is a natural phenylpropene found in several plants, which are widely used for flavoring foods and treating diseases. Previous studies have demonstrated that α-asarone has many pharmacological functions, while some reports indicated its toxicity. However, little is known about its cardiovascular effects. This study investigated developmental toxicity of α-asarone in zebrafish, especially the cardiotoxicity. Zebrafish embryos were exposed to different concentrations of α-asarone (1, 3, 5, 10, and 30 μM). Developmental toxicity assessments revealed that α-asarone did not markedly affect mortality and hatching rate. In contrast, there was a concentration-dependent increase in malformation rate of zebrafish treated with α-asarone. The most representative cardiac defects were increased heart malformation rate, pericardial edema areas, sinus venosus-bulbus arteriosus distance, and decreased heart rate. Notably, we found that α-asarone impaired the cardiac function of zebrafish by prolonging the mean QTc duration and causing T-wave abnormalities. The expressions of cardiac development-related key transcriptional regulators tbx5, nkx2.5, hand2, and gata5 were all changed under α-asarone exposure. Further investigation addressing the mechanism indicated that α-asarone triggered apoptosis mainly in the heart region of zebrafish. Moreover, the elevated expression of puma, cyto C, afap1, caspase 3, and caspase 9 in treated zebrafish suggested that mitochondrial apoptosis is likely to be the main reason for α-asarone induced cardiotoxicity. These findings revealed the cardiac developmental toxicity of α-asarone, expanding our knowledge about the toxic effect of α-asarone on living organisms.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping