Embryonic stem cell-derived cardiomyocytes as a model system to study cardioprotective effects of dexamethasone in doxorubicin cardiotoxicity.
Embryonic stem cell (ESC)-derived beating cardiomyocytes may be considered as a suitable model for in vitro assessment of pharmacological and toxicological studies. In this model, laboratory animals are not required. In addition, physiological functions, such as heart beat, are assessed rather than single parameters such as cell viability. Here we report that doxorubicin (DOX) cardiotoxicity on mouse ESC-derived beating cardiomyocytes can be ameliorated by treatment with dexamethasone (DEX) when DEX is administrated only before DOX and not in combination with DOX. DEX effect appears to be mediated via glucocorticoid receptor and increases cardiomyocyte-specific gene expression. Cardiotoxicity of DOX can be augmented by calcium channel blocker, verapamil (VER) which also decreases the expression of cardiac gene markers. This model provides us with a clinical suggestion which proposes that the beneficial effect of DEX is obtained when DEX was added before DOX administration.
Farokhpour
Mahboubeh
M
Department of Cell and Molecular Biology, Royan Institute for Animal Biotechnology, Esfahan, Iran.
Karbalaie
Khadijeh
K
Tanhaei
Somayeh
S
Nematollahi
Marzeyeh
M
Etebari
Mahmoud
M
Sadeghi
Hamid Mirmohammad
HM
Nasr-Esfahani
Mohammad Hossein
MH
Baharvand
Hossein
H
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D003603:Cytotoxins / Q000633:toxicity; D003907:Dexamethasone / Q000494:pharmacology*; D004317:Doxorubicin / Q000633:toxicity*; D053595:Embryonic Stem Cells / Q000166:cytology*; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects; D051379:Mice; D008954:Models, Biological; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014700:Verapamil / Q000633:toxicity
D000903:Antibiotics, Antineoplastic; D003603:Cytotoxins; D005938:Glucocorticoids; D020011:Protective Agents; D003907:Dexamethasone; D004317:Doxorubicin; D014700:Verapamil