PUBLICATION

The toxic effect of Amiodarone on valve formation in the developing heart of zebrafish embryos

Authors
Chen, Y.H., Hsu, R.J., Chen, T.Y., Huang, Y.K., Lee, H.C., Hu, S.C., Harn, H.J., Jeng, J.R., Sun, C.K., Lin, S.Z., and Tsai, H.J.
ID
ZDB-PUB-120111-33
Date
2012
Source
Reproductive toxicology (Elmsford, N.Y.)   33(2): 233-244 (Journal)
Registered Authors
Tsai, Huai-Jen
Keywords
none
MeSH Terms
  • Amiodarone/toxicity*
  • Animals
  • Anti-Arrhythmia Agents/toxicity*
  • Antigens, CD/genetics
  • Cadherins/genetics
  • Embryo, Nonmammalian/drug effects
  • Embryo, Nonmammalian/embryology
  • Heart Valves/drug effects*
  • Heart Valves/embryology
  • Teratogens/toxicity*
  • Versicans/genetics
  • Zebrafish/embryology
  • Zebrafish Proteins/genetics
PubMed
22227723 Full text @ Reprod. Toxicol.
Abstract

Background

Amiodarone is a class D drug given to treat arrhythmia, including pregnant women, but its effects on the developing heart have not been studied. Although some studies have suggested that this drug is safe for fetuses, they have been conducted on mothers with fetuses at or beyond six months of gestational age.

Results

The occurrence of valve defect was positively proportional to Amiodarone concentrations over 9 μM, but not lower than 6 μM. Ectopic overexpression of versican was observed at the atrioventricular canal of the Amiodarone-treated embryos at 15 μM (EC50). VE-cadherin (cdh5), normally downregulated at the endocardial cushion, was also ectopically overexpressed in the Amiodarone-treated embryos. Knockdown of either versican or cdh5 in the Amiodarone-treated embryos could rescue the valve defect caused by Amiodarone.

Conclusions

By inducing versican ectopical overexpression, leading, in turn, to cdh5 ectopical overexpression, Amiodarone treatment causes failure of cardiac valve formation in zebrafish embryos.

Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes