Document Detail


Embryonic stem cell-derived cardiomyocytes as a model system to study cardioprotective effects of dexamethasone in doxorubicin cardiotoxicity.
MedLine Citation:
PMID:  19596060     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Mahboubeh Farokhpour; Khadijeh Karbalaie; Somayeh Tanhaei; Marzeyeh Nematollahi; Mahmoud Etebari; Hamid Mirmohammad Sadeghi; Mohammad Hossein Nasr-Esfahani; Hossein Baharvand
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-07-22
Journal Detail:
Title:  Toxicology in vitro : an international journal published in association with BIBRA     Volume:  23     ISSN:  1879-3177     ISO Abbreviation:  Toxicol In Vitro     Publication Date:  2009 Oct 
Date Detail:
Created Date:  2009-10-02     Completed Date:  2009-12-14     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8712158     Medline TA:  Toxicol In Vitro     Country:  England    
Other Details:
Languages:  eng     Pagination:  1422-8     Citation Subset:  IM    
Affiliation:
Department of Cell and Molecular Biology, Royan Institute for Animal Biotechnology, Esfahan, Iran.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibiotics, Antineoplastic / toxicity*
Cytotoxins / toxicity
Dexamethasone / pharmacology*
Doxorubicin / toxicity*
Embryonic Stem Cells / cytology*
Gene Expression Regulation / drug effects
Glucocorticoids / pharmacology*
Heart / drug effects
Mice
Models, Biological*
Myocardium / metabolism
Myocytes, Cardiac / drug effects*,  metabolism
Protective Agents / pharmacology*
Reverse Transcriptase Polymerase Chain Reaction
Verapamil / toxicity
Chemical
Reg. No./Substance:
0/Antibiotics, Antineoplastic; 0/Cytotoxins; 0/Glucocorticoids; 0/Protective Agents; 23214-92-8/Doxorubicin; 50-02-2/Dexamethasone; 52-53-9/Verapamil

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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