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Comparative effects of sodium channel blockers in short term rat whole embryo culture.
Toxicol Appl Pharmacol. 2013 Oct 15; 272(2):306-12.TA

Abstract

This study was undertaken to examine the effect on the rat embryonic heart of two experimental drugs (AZA and AZB) which are known to block the sodium channel Nav1.5, the hERG potassium channel and the l-type calcium channel. The sodium channel blockers bupivacaine, lidocaine, and the l-type calcium channel blocker nifedipine were used as reference substances. The experimental model was the gestational day (GD) 13 rat embryo cultured in vitro. In this model the embryonic heart activity can be directly observed, recorded and analyzed using computer assisted image analysis as it responds to the addition of test drugs. The effect on the heart was studied for a range of concentrations and for a duration up to 3h. The results showed that AZA and AZB caused a concentration-dependent bradycardia of the embryonic heart and at high concentrations heart block. These effects were reversible on washout. In terms of potency to cause bradycardia the compounds were ranked AZB>bupivacaine>AZA>lidocaine>nifedipine. Comparison with results from previous studies with more specific ion channel blockers suggests that the primary effect of AZA and AZB was sodium channel blockage. The study shows that the short-term rat whole embryo culture (WEC) is a suitable system to detect substances hazardous to the embryonic heart.

Authors+Show Affiliations

Department of Pharmaceutical Biosciences, Uppsala University, Sweden. Electronic address: Mats.Nilsson@farmbio.uu.se.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

23845595

Citation

Nilsson, Mats F., et al. "Comparative Effects of Sodium Channel Blockers in Short Term Rat Whole Embryo Culture." Toxicology and Applied Pharmacology, vol. 272, no. 2, 2013, pp. 306-12.
Nilsson MF, Sköld AC, Ericson AC, et al. Comparative effects of sodium channel blockers in short term rat whole embryo culture. Toxicol Appl Pharmacol. 2013;272(2):306-12.
Nilsson, M. F., Sköld, A. C., Ericson, A. C., Annas, A., Villar, R. P., Cebers, G., Hellmold, H., Gustafson, A. L., & Webster, W. S. (2013). Comparative effects of sodium channel blockers in short term rat whole embryo culture. Toxicology and Applied Pharmacology, 272(2), 306-12. https://doi.org/10.1016/j.taap.2013.06.023
Nilsson MF, et al. Comparative Effects of Sodium Channel Blockers in Short Term Rat Whole Embryo Culture. Toxicol Appl Pharmacol. 2013 Oct 15;272(2):306-12. PubMed PMID: 23845595.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparative effects of sodium channel blockers in short term rat whole embryo culture. AU - Nilsson,Mats F, AU - Sköld,Anna-Carin, AU - Ericson,Ann-Christin, AU - Annas,Anita, AU - Villar,Rodrigo Palma, AU - Cebers,Gvido, AU - Hellmold,Heike, AU - Gustafson,Anne-Lee, AU - Webster,William S, Y1 - 2013/07/08/ PY - 2012/11/09/received PY - 2013/06/16/revised PY - 2013/06/21/accepted PY - 2013/7/13/entrez PY - 2013/7/13/pubmed PY - 2013/12/16/medline KW - Cardiac function KW - Drugs during pregnancy KW - Embryonic physiology KW - Hazard identification KW - Sodium channel blocker SP - 306 EP - 12 JF - Toxicology and applied pharmacology JO - Toxicol. Appl. Pharmacol. VL - 272 IS - 2 N2 - This study was undertaken to examine the effect on the rat embryonic heart of two experimental drugs (AZA and AZB) which are known to block the sodium channel Nav1.5, the hERG potassium channel and the l-type calcium channel. The sodium channel blockers bupivacaine, lidocaine, and the l-type calcium channel blocker nifedipine were used as reference substances. The experimental model was the gestational day (GD) 13 rat embryo cultured in vitro. In this model the embryonic heart activity can be directly observed, recorded and analyzed using computer assisted image analysis as it responds to the addition of test drugs. The effect on the heart was studied for a range of concentrations and for a duration up to 3h. The results showed that AZA and AZB caused a concentration-dependent bradycardia of the embryonic heart and at high concentrations heart block. These effects were reversible on washout. In terms of potency to cause bradycardia the compounds were ranked AZB>bupivacaine>AZA>lidocaine>nifedipine. Comparison with results from previous studies with more specific ion channel blockers suggests that the primary effect of AZA and AZB was sodium channel blockage. The study shows that the short-term rat whole embryo culture (WEC) is a suitable system to detect substances hazardous to the embryonic heart. SN - 1096-0333 UR - https://www.unboundmedicine.com/medline/citation/23845595/Comparative_effects_of_sodium_channel_blockers_in_short_term_rat_whole_embryo_culture_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0041-008X(13)00296-2 DB - PRIME DP - Unbound Medicine ER -