title: Carbamazepine toxic effects in chick cardiomyocyte micromass culture and embryonic stem cell derived cardiomyocyte systems--possible protective role of antioxidants.
abstract: The use of carbamazepine (CBZ) during pregnancy increases cardiovascular anomalies. In this study CBZ developmental cardiotoxic effects were evaluated using chick cardiomyocyte micromass (MM) culture and mouse embryonic stem cells derived cardiomyocyte (ESDC) systems. In MM culture, CBZ only inhibited the cardiomyocyte contractile activity, while in ESDC it completely ceased the contractile activity at 200 μM with decreased cell viability and protein content. The antioxidant superoxide dismutase (SOD) supplement in MM and ascorbic acid (AA) in ESDC showed protective effects on CBZ toxicity, but elevated levels of reactive oxygen species (ROS) production were recorded with CBZ treatment only in ESDC. CBZ has also affected cardiac connexin 43 expression in both in vitro systems. Our results indicated CBZ induced ROS stress as mechanism of developmental cardiotoxicity at early stage of cardiogenesis in ESDC system compared to MM system's differentiated cells. These toxic effects can be negated by using antioxidant agent.
authors.affiliation: School of Life Sciences, Queen's Medical Centre, University of Nottingham, Nottingham, NG7 2UH, UK. Electronic address: wasay9710@yahoo.com.
authors.forename: W M Shaikh
authors.initials: WM
authors.lastname: Qureshi
authors.affiliation: School of Life Sciences, Queen's Medical Centre, University of Nottingham, Nottingham, NG7 2UH, UK. Electronic address: samreen_memon@yahoo.co.uk.
authors.forename: S
authors.initials: S
authors.lastname: Memon
authors.affiliation: School of Life Sciences, Queen's Medical Centre, University of Nottingham, Nottingham, NG7 2UH, UK. Electronic address: mbzmll1@exmail.nottingham.ac.uk.
authors.forename: M L
authors.initials: ML
authors.lastname: Latif
authors.affiliation: School of Life Sciences, Queen's Medical Centre, University of Nottingham, Nottingham, NG7 2UH, UK. Electronic address: michael.garle@nottingham.ac.uk.
authors.forename: M J
authors.initials: MJ
authors.lastname: Garle
authors.affiliation: School of Life Sciences, Queen's Medical Centre, University of Nottingham, Nottingham, NG7 2UH, UK.
authors.forename: T L
authors.initials: TL
authors.lastname: Parker
authors.affiliation: School of Life Sciences, Queen's Medical Centre, University of Nottingham, Nottingham, NG7 2UH, UK. Electronic address: Margaret.Pratten@nottingham.ac.uk.
authors.forename: M K
authors.initials: MK
authors.lastname: Pratten
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002220:Carbamazepine / Q000633:toxicity*; D002645:Chickens; D018031:Connexin 43 / Q000032:analysis; D053595:Embryonic Stem Cells / Q000166:cytology; D051379:Mice; D032383:Myocytes, Cardiac / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D018031:Connexin 43; D017382:Reactive Oxygen Species; D002220:Carbamazepine; D013482:Superoxide Dismutase
keywords: Ascorbic acid; Carbamazepine; Cardiomyocyte; Chick micromass culture; Embryonic stem cells; Reactive oxygen species; Teratogenicity