Embryonic stem cell-derived cardiomyocytes as a model system to study cardioprotective effects of dexamethasone in doxorubicin cardiotoxicity

被引：20

作者：

Farokhpour, Mahboubeh ^{[2
,3
]}

Karbalaie, Khadijeh ^{[1
,2
]}

Tanhaei, Somayeh ^{[1
,2
]}

Nematollahi, Marzeyeh ^{[1
,2
]}

Etebari, Mahmoud ^{[3
]}

Sadeghi, Hamid Mirmohammad ^{[3
]}

Nasr-Esfahani, Mohammad Hossein ^{[1
,2
]}

Baharvand, Hossein ^{[1
,4
]}

机构：

[1] Royan Inst Stem Cell Biol & Technol, ACECR, Dept Stem Cells & Dev Biol, Tehran, Iran

[2] Royan Inst Anim Biotechnol, Dept Cell & Mol Biol, Esfahan, Iran

[3] Univ Isfahan, Sch Pharm & Pharmaceut Sci, Dept Pharmacol, Esfahan, Iran

[4] Univ Sci & Culture, ACECR, Dept Dev Biol, Tehran, Iran

来源：

TOXICOLOGY IN VITRO | 2009年 / 23卷 / 07期

关键词：

Embryonic stem cells; Cardiomyocyte differentiation; Cytotoxicity; Doxorubicin; Dexamethasone; Mifepristone; Verapamil; MUSCLE GENE-EXPRESSION; GENERATION; DIFFERENTIATION; EMBRYOTOXICITY; MOUSE; VALIDATION; INDUCTION; TOXICITY; OPTIMIZATION; FIBROBLASTS;

D O I：

10.1016/j.tiv.2009.07.008

中图分类号：

R99 [毒物学（毒理学）];

学科分类号：

100405 ;

摘要：

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. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：1422 / 1428

页数：7

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