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

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

► The valve defect was found in zebrafish embryos treated with Amiodarone over 9 μM.
► Ectopic overexpression of versican was observed in the Amiodarone-treated embryos.
► Ectopic overexpression of VE-cadherin (cdh5) was also observed.
► Knockdown of versican or cdh5 could rescue the valve defect caused by Amiodarone.
► By inducing versican and cdh5 overexpression, Amiodarone causes cardiac valve defect.