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

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α-asarone induces cardiac defects and QT prolongation through mitochondrial apoptosis pathway in zebrafish. / Shang, Xueliang; Ji, Xiuna; Dang, Jiao; Wang, Lizhen; Sun, Chen; Liu, Kechun; Sik, Attila; Jin, Meng.

In: Toxicology Letters, Vol. 324, 15.05.2020, p. 1-11.

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Shang, Xueliang ; Ji, Xiuna ; Dang, Jiao ; Wang, Lizhen ; Sun, Chen ; Liu, Kechun ; Sik, Attila ; Jin, Meng. / α-asarone induces cardiac defects and QT prolongation through mitochondrial apoptosis pathway in zebrafish. In: Toxicology Letters. 2020 ; Vol. 324. pp. 1-11.

Bibtex

@article{485e5f1300a84281b4b79d6fe24916ab,
title = "α-asarone induces cardiac defects and QT prolongation through mitochondrial apoptosis pathway in zebrafish",
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.",
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",
author = "Xueliang Shang and Xiuna Ji and Jiao Dang and Lizhen Wang and Chen Sun and Kechun Liu and Attila Sik and Meng Jin",
note = "Copyright {\textcopyright} 2020 Elsevier B.V. All rights reserved.",
year = "2020",
month = may,
day = "15",
doi = "10.1016/j.toxlet.2020.02.003",
language = "English",
volume = "324",
pages = "1--11",
journal = "Toxicology Letters",
issn = "0378-4274",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - α-asarone induces cardiac defects and QT prolongation through mitochondrial apoptosis pathway in zebrafish

AU - Shang, Xueliang

AU - Ji, Xiuna

AU - Dang, Jiao

AU - Wang, Lizhen

AU - Sun, Chen

AU - Liu, Kechun

AU - Sik, Attila

AU - Jin, Meng

N1 - Copyright © 2020 Elsevier B.V. All rights reserved.

PY - 2020/5/15

Y1 - 2020/5/15

N2 - 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.

AB - 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.

KW - Abnormalities, Drug-Induced/etiology

KW - Animals

KW - Anisoles/toxicity

KW - Apoptosis/drug effects

KW - Cardiotoxicity/etiology

KW - Electrocardiography/drug effects

KW - Embryo, Nonmammalian/drug effects

KW - Heart Defects, Congenital/chemically induced

KW - Mitochondria, Heart/drug effects

KW - Zebrafish

U2 - 10.1016/j.toxlet.2020.02.003

DO - 10.1016/j.toxlet.2020.02.003

M3 - Article

C2 - 32035120

VL - 324

SP - 1

EP - 11

JO - Toxicology Letters

JF - Toxicology Letters

SN - 0378-4274

ER -