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Sca‐1 positive cells are more sensitive than adult rat cardiomyocytes to doxorubicin‐induced changes
Author(s) -
Ludke Ana,
Sharma Anita K,
Bagchi Ashim K,
Singal Pawan K
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.693.3
Subject(s) - oxidative stress , viability assay , doxorubicin , pharmacology , mtt assay , progenitor cell , cardiotoxicity , stem cell , myocyte , vitamin e , cell , vitamin c , chemistry , medicine , antioxidant , biology , endocrinology , microbiology and biotechnology , toxicity , biochemistry , chemotherapy
Cardiac progenitor cells in the adult heart have recently been implicated in Doxorubicin (Dox)‐induced cardiomyopathy. This study compared the Dox‐induced changes, mediated by oxidative stress, in cardiac stem cells expressing antigen‐1 (Sca‐1 pos) and in cardiomyocytes isolated from adult Sprague‐Dawley rat hearts. Sca‐1 pos cells as well as cardiomyocytes were incubated for 24h with different concentrations of Dox (0.01–10 μM), with and without Vitamin C (25 μM) ‐ a potent antioxidant. Using the same number of cells, an analysis of cell viability (MTT assay), cell injury (AK release), oxidative stress (DCFDA), and ATP levels was performed. Sca‐1 pos cells showed significant decrease in viability and ATP levels and increase in oxidative stress and cell injury at all doses of Dox. Cardiomyocytes were affected only at doses higher than 0.1 μM and significantly less change in these parameters were seen as compared to the Sca‐1 pos cells. Vitamin C was able to mitigate Dox‐induced changes in both cell types. It is suggested that cardiac progenitor cells are more susceptible to Dox‐induced damage in comparison to cardiomyocytes which appear to be mediated by oxidative stress. These findings contribute to a better understanding of the delayed vulnerability of the heart after a prolonged Dox administration. (Supported by Manitoba Health Research Council).