Evaluation of bupropion hydrochloride developmental cardiotoxic effects in chick cardiomyocyte micromass culture and stem cell derived cardiomyocyte systems

Birth Defects Res B Dev Reprod Toxicol. 2014 Oct;101(5):371-8. doi: 10.1002/bdrb.21121. Epub 2014 Sep 23.

Abstract

The use of antidepressant drug bupropion hydrochloride (BPN) during pregnancy results in increased cardiovascular anomalies. In this study, BPN developmental cardiotoxic effects in in vitro system were evaluated using chick cardiomyocyte micromass (MM) culture system and mouse embryonic stem cell derived cardiomyocyte (ESDC) system. In MM system, the cardiomyocyte contractile activity significantly decreased only at BPN 200 μM, while in ESDC system BPN concentration above 75 μM resulted in decreased contractile activity. The increase in drug concentration also affected the cardiomyocyte viability and total cellular protein content in both systems, but in ESDC system the cell viability failed to attain significant difference. The drug failed to induce reactive oxygen species production in both systems, but has affected the cardiac connexin43 expression especially in MM system. We observed that BPN showed developmental cardiotoxic effects irrespective of the stage of cardiac development in both in vitro systems.

Keywords: Bupropion hydrochloride; cardiomyocyte; connexin43; embryonic stem cell; micromass; teratology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antidepressive Agents, Second-Generation / pharmacology*
  • Bupropion / adverse effects
  • Bupropion / pharmacology*
  • Cardiotoxins / pharmacology*
  • Cell Differentiation / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Chickens
  • Connexin 43
  • Embryonic Stem Cells / cytology
  • Female
  • Heart / embryology
  • Mice
  • Myocardial Contraction / drug effects*
  • Myocytes, Cardiac / cytology*
  • Pregnancy
  • Reactive Oxygen Species / metabolism
  • Stem Cells

Substances

  • Antidepressive Agents, Second-Generation
  • Cardiotoxins
  • Connexin 43
  • GJA1 protein, human
  • Reactive Oxygen Species
  • Bupropion