INTRODUCTION: It has been proposed that the analysis of heart rate in zebrafish embryos can be used to assess the potential effects of compounds on hERG. The purpose of this study was to investigate the effect of compounds on the heart rate and atrioventricular dissociation in zebrafish. The compounds investigated were chosen based on the association or lack of association with QTc prolongation in the clinic. METHODS: Three-day-old embryos were incubated in buffered embryo medium. On the day of the study, fish were placed in a petri dish containing 5.0 mL of embryo medium and 125 mg/L MS-222 anesthetic. Drugs to be tested were added to the medium from a stock solution to achieve the desired target concentration. Ten fish were incubated in each concentration of drug for 80 min. Beat rates of the atrium and ventricle were recorded after the incubation by counting beats of the respective chambers using standard brightfield stereomicroscopy. RESULTS: All of the compounds associated with QT prolongation induced dissociation between the atrium and ventricular rates except D,L-sotalol and procainamide. The concentrations that induced dissociation tended to be higher than the hERG IC50. None of the negative control compounds caused atrioventricular dissociation at clinically efficacious concentrations. DISCUSSION: In conclusion, the present data demonstrate that zebrafish can be utilized to assess the effects of chemicals on hERG. However, the practical use of this assay may be difficult because of the high concentrations that must be reached to see those pharmacological effects.
INTRODUCTION: It has been proposed that the analysis of heart rate in zebrafish embryos can be used to assess the potential effects of compounds on hERG. The purpose of this study was to investigate the effect of compounds on the heart rate and atrioventricular dissociation in zebrafish. The compounds investigated were chosen based on the association or lack of association with QTc prolongation in the clinic. METHODS: Three-day-old embryos were incubated in buffered embryo medium. On the day of the study, fish were placed in a petri dish containing 5.0 mL of embryo medium and 125 mg/L MS-222 anesthetic. Drugs to be tested were added to the medium from a stock solution to achieve the desired target concentration. Ten fish were incubated in each concentration of drug for 80 min. Beat rates of the atrium and ventricle were recorded after the incubation by counting beats of the respective chambers using standard brightfield stereomicroscopy. RESULTS: All of the compounds associated with QT prolongation induced dissociation between the atrium and ventricular rates except D,L-sotalol and procainamide. The concentrations that induced dissociation tended to be higher than the hERG IC50. None of the negative control compounds caused atrioventricular dissociation at clinically efficacious concentrations. DISCUSSION: In conclusion, the present data demonstrate that zebrafish can be utilized to assess the effects of chemicals on hERG. However, the practical use of this assay may be difficult because of the high concentrations that must be reached to see those pharmacological effects.
Authors: Ming Wai Hung; Zai Jun Zhang; Shang Li; Benson Lei; Shuai Yuan; Guo Zhen Cui; Pui Man Hoi; Kelvin Chan; Simon Ming Yuen Lee Journal: Evid Based Complement Alternat Med Date: 2012-08-05 Impact factor: 2.629
Authors: Rayk Stengel; Eric Rivera-Milla; Nirakar Sahoo; Christina Ebert; Frank Bollig; Stefan H Heinemann; Roland Schönherr; Christoph Englert Journal: J Biol Chem Date: 2012-08-27 Impact factor: 5.157
Authors: Sundeep Singh Dhillon; Eva Dóró; István Magyary; Stuart Egginton; Attila Sík; Ferenc Müller Journal: PLoS One Date: 2013-04-08 Impact factor: 3.240