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

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 de...

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Bibliographic Details
Published in:Birth defects research. Part B. Developmental and reproductive toxicology 2014-10, Vol.101 (5), p.371-378
Main Authors: Shaikh Qureshi, W. M., Latif, Muhammad Liaque, Parker, Terry L., Pratten, Margaret K.
Format: Article
Language:English
Subjects:
Animals
Antidepressive Agents, Second-Generation - pharmacology
Bupropion - adverse effects
Bupropion - pharmacology
Bupropion hydrochloride
cardiomyocyte
Cardiotoxins - pharmacology
Cell Differentiation - drug effects
Cell Survival - drug effects
Cells, Cultured
Chickens
Connexin 43
connexin43
embryonic stem cell
Embryonic Stem Cells - cytology
Female
Heart - embryology
Mice
micromass
Myocardial Contraction - drug effects
Myocytes, Cardiac - cytology
Pregnancy
Reactive Oxygen Species - metabolism
Stem Cells
teratology
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Summary: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
ISSN:1542-9733
1542-9741
DOI:10.1002/bdrb.21121