title: 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.
authors.affiliation: School of Biomedical Sciences, Queen's Medical Centre, University of Nottingham, Nottinghamshire, United Kingdom.
authors.forename: W M
authors.initials: WM
authors.lastname: Shaikh Qureshi
authors.forename: Muhammad Liaque
authors.initials: ML
authors.lastname: Latif
authors.forename: Terry L
authors.initials: TL
authors.lastname: Parker
authors.forename: Margaret K
authors.initials: MK
authors.lastname: Pratten
mesh_terms: D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D016642:Bupropion / Q000009:adverse effects / Q000494:pharmacology*; D054715:Cardiotoxins / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002645:Chickens; D018031:Connexin 43; D053595:Embryonic Stem Cells / Q000166:cytology; D005260:Female; D006321:Heart / Q000196:embryology; D051379:Mice; D009200:Myocardial Contraction / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000166:cytology*; D011247:Pregnancy; D017382:Reactive Oxygen Species / Q000378:metabolism; D013234:Stem Cells
chemical_list: D018687:Antidepressive Agents, Second-Generation; D054715:Cardiotoxins; D018031:Connexin 43; C500216:GJA1 protein, human; D017382:Reactive Oxygen Species; D016642:Bupropion
keywords: Bupropion hydrochloride; cardiomyocyte; connexin43; embryonic stem cell; micromass; teratology