The toxic effect of Amiodarone on valve formation in the developing heart of zebrafish embryos.
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 (EC(50)). 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.
Institute of Medical Sciences, Buddhist Tzu Chi University, Taiwan.
Ying-Hsin
YH
Chen
Hung-Chieh
HC
Lee
Ren-Jun
RJ
Hsu
Ta-Yuan
TY
Chen
Yu-Kai
YK
Huang
Hao-Chan
HC
Lo
Sheng-Chuan
SC
Hu
Horng-Jyh
HJ
Harn
Jing-Ren
JR
Jeng
Chi-Kuang
CK
Sun
Shinn-Zong
SZ
Lin
Huai-Jen
HJ
Tsai
D000638:Amiodarone / Q000633:toxicity*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000633:toxicity*; D015703:Antigens, CD / Q000235:genetics; D015820:Cadherins / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000196:embryology; D006351:Heart Valves / Q000187:drug effects* / Q000196:embryology; D013723:Teratogens / Q000633:toxicity*; D053675:Versicans / Q000235:genetics; D015027:Zebrafish / Q000196:embryology; D029961:Zebrafish Proteins / Q000235:genetics; D000099152:Cadherin 5
D000638:Amiodarone; D000889:Anti-Arrhythmia Agents; D015703:Antigens, CD; D015820:Cadherins; D013723:Teratogens; D053675:Versicans; D029961:Zebrafish Proteins; D000099152:Cadherin 5