α-asarone induces cardiac defects and QT prolongation through mitochondrial apoptosis pathway in zebrafish

Xueliang Shang, Xiuna Ji, Jiao Dang, Lizhen Wang, Chen Sun, Kechun Liu, Attila Sik, Meng Jin

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4 Citations (Scopus)
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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 languageEnglish
Pages (from-to)1-11
Number of pages11
JournalToxicology Letters
Volume324
Early online date5 Feb 2020
DOIs
Publication statusPublished - 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

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