Lithium carbonate teratogenic effects in chick cardiomyocyte micromass system and mouse embryonic stem cell derived cardiomyocyte--possible protective role of myo-inositol.
The drug lithium carbonate (Li2CO3) use during pregnancy increases the possibility of cardiovascular anomalies. The earlier studies confirm its phosphatidylinositol cycle (PI) inhibition and Wnt pathways mimicking properties, which might contribute to its teratogenic effects. In this study the toxic effects of Li2CO3 in chick embryonic cardiomyocyte micromass system (MM) and embryonic stem cell derived cardiomyocyte (ESDC) were evaluated, with possible protective role of myo-inositol. In MM system the Li2CO3 did not alter the toxicity estimation endpoints, whereas in ESDC system the cardiomyocytes contractile activity stopped at 1500 μM and above with significant increase in total cellular protein contents. In ESDC system when myo-inositol was added along with Li2CO3 to continue PI cycle, the contractile activity was recovered with decreased protein content. The lithium toxic effects depend on the role of PI cycle at particular stage of cardiogenesis, while relation between myo-inositol and reduced cellular protein contents remains unknown.
Centre for Integrated Systems Biology and Medicine, School of Biomedical Sciences, Queen's Medical Centre, University of Nottingham, Nottinghamshire NG7 2UH, UK. Electronic address: wasay9710@yahoo.com.
W M Shaikh
WM
Qureshi
Centre for Integrated Systems Biology and Medicine, School of Biomedical Sciences, Queen's Medical Centre, University of Nottingham, Nottinghamshire NG7 2UH, UK. Electronic address: mbzmll1@exmail.nottingham.ac.uk.
M L
ML
Latif
Centre for Integrated Systems Biology and Medicine, School of Biomedical Sciences, Queen's Medical Centre, University of Nottingham, Nottinghamshire NG7 2UH, UK. Electronic address: terry.parker@nottingham.ac.uk.
T L
TL
Parker
Centre for Integrated Systems Biology and Medicine, School of Biomedical Sciences, Queen's Medical Centre, University of Nottingham, Nottinghamshire NG7 2UH, UK. Electronic address: Margaret.Pratten@nottingham.ac.uk.
M K
MK
Pratten
D000818:Animals; D018692:Antimanic Agents / Q000633:toxicity*; D002642:Chick Embryo; D053595:Embryonic Stem Cells / Q000187:drug effects*; D023381:Endpoint Determination; D007294:Inositol / Q000494:pharmacology*; D016651:Lithium Carbonate / Q000037:antagonists & inhibitors / Q000633:toxicity*; D051379:Mice; D032383:Myocytes, Cardiac / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013723:Teratogens / Q000633:toxicity*
D018692:Antimanic Agents; D017382:Reactive Oxygen Species; D013723:Teratogens; D016651:Lithium Carbonate; D007294:Inositol
Cardiomyocytes; Chick micromass; Embryonic stem cells; Lithium carbonate; Myo-inositol; Teratogenic