Evaluation of Bupropion Hydrochloride Developmental Cardiotoxic Effects in Chick Cardiomyocyte Micromass Culture and stem cell derived Cardiomyocyte Systems

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.

Electrocardiographic Effects of Bupropion Toxicity Suggesting Dysfunction of the Gap Junction or Connexin 43

“…Additionally, there is evidence that the permeability of Cx-43 gap junctions is regulated by the cell’s intracellular calcium concentration [ 14 , 15 ]. Literature suggests that bupropion has a role as a calcium channel inhibitor, it can be speculated that the bupropion serves to increase intracellular Ca 2+ concentration via the blocking of calcium-related hemi channels, thus causing inhibition and closure of Cx-43 gap junctions [ 15 , 16 ].…”