例如:"lncRNA", "apoptosis", "WRKY"

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

Toxicol. Lett.2020 May 15;324:1-11. Epub 2020 Feb 05
Xueliang Shang 1 , Xiuna Ji 2 , Jiao Dang 2 , Lizhen Wang 2 , Chen Sun 2 , Kechun Liu 2 , Attila Sik 3 , Meng Jin 4
Xueliang Shang 1 , Xiuna Ji 2 , Jiao Dang 2 , Lizhen Wang 2 , Chen Sun 2 , Kechun Liu 2 , Attila Sik 3 , Meng Jin 4
+ et al

[No authors listed]

Author information
  • 1 School of Psychology, North China University of Science and Technology, 21 Bohai Road, Tang'shan 063210, Hebei Province, PR China.
  • 2 Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), 28789 East Jingshi Road, Ji'nan 250103, Shandong Province, PR China; Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, 28789 East Jingshi Road, Ji'nan 250103, Shandong Province, PR China.
  • 3 Institute of Physiology, Medical School, University of Pecs, Pecs H-7624, Hungary; Szentagothai Research Centre, University of Pecs, Pecs H-7624, Hungary; Institute of Clinical Sciences, Medical School, University of Birmingham, Birmingham B15 2TT, United Kingdom.
  • 4 Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), 28789 East Jingshi Road, Ji'nan 250103, Shandong Province, PR China; Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, 28789 East Jingshi Road, Ji'nan 250103, Shandong Province, PR China. Electronic address: mjin1985@hotmail.com.

摘要


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: Apoptosis, Cardiotoxicity, QT duration, T-wave, Zebrafish