Bengtsson, Ewert
- Centre for Image Analysis, Swedish University of Agricultural Sciences
Abstract
Drugs blocking the potassium current IKr of the heart (via hERG channel-inhibition) have the potential to cause hypoxia-related teratogenic effects. However, this activity may be missed in conventional teratology studies because repeat dosing may cause resorptions. The aim of the present study was to investigate an alternative protocol to reveal the teratogenic potential of IKr-blocking drugs. The IKr blocker astemizole, given as a single dose (80mg/kg) on gestation day (GD) 13 to pregnant rats caused digital defects. In whole rat embryo culture (2h) on GD 13, astemizole caused a decrease in embryonic heart rate at 20nM, and arrhythmias at 200-400nM. Cetirizine, without IKr-blocking properties, did not affect the rat embryonic heart in vitro. The present study shows that single dose testing on sensitive days of development, together with whole embryo culture, can be a useful methodology to better characterize the teratogenic potential of IKr-blocking drugs
Keywords
Astemizole; hERG channel; IKr; Teratogenicity; Hypoxia; Embryonic cardiac adverse effects
Published in
Reproductive Toxicology
2010, volume: 29, number: 2, pages: 156-163
Publisher: Elsevier
SLU Authors
UKÄ Subject classification
Other Clinical Medicine
Pharmacology and Toxicology
Publication identifier
- DOI: https://doi.org/10.1016/j.reprotox.2010.01.014
Permanent link to this page (URI)
https://res.slu.se/id/publ/31863