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.
Original language | English |
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Pages (from-to) | 1-11 |
Number of pages | 11 |
Journal | Toxicology Letters |
Volume | 324 |
Early online date | 5 Feb 2020 |
DOIs | |
Publication status | Published - 15 May 2020 |
Bibliographical note
Copyright © 2020 Elsevier B.V. All rights reserved.Keywords
- 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
- Zebrafish