51. Doxorubicin-associated late developing cardiomyopathy may be related to the depletion of cardiac primitive cells pool in the adult human heart
- Author
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DI MEGLIO, FRANCA, NURZYNSKA, DARIA ANNA, CASTALDO, CLOTILDE, MIRAGLIA, RITA, MONTAGNANI, STEFANIA, De Angelis A., Piegari A., Bancone C., DI MEGLIO, Franca, Nurzynska, DARIA ANNA, Castaldo, Clotilde, De Angelis, A., Piegari, A., Miraglia, Rita, Bancone, C., and Montagnani, Stefania
- Abstract
The cumulative dose-dependent toxicity of doxorubicin, with the late development of the chronic heart failure that does not respond to digitalis, imposes serious limits on cancer treatment and often leads to heart transplantation in relatively young patients. Known studies of the mechanisms of doxorubicin toxicity focused on cardiomyocytes damage. According to the new notion of cardiac tissue biology, cardiac primitive cells are considered to provide the adult heart with a substantial growth reserve determining the function of the heart throughout life. Hence, numerous factors that can influence the subtle balance between cardiac primitive cells death and survival, can be implicated in the development and progression of cardiomyopathy and heart failure. The scope of the study was to examine the effects of doxorubicin on human adult CD117-positive cardiac primitive cells in vitro. Moreover, the role of dexrazoxane, a chelating agent with cardioprotective action, was revisited with respect to the reduction of doxorubicin toxicity on cardiac primitive cells. CD117-positive cells were incubated with increasing concentrations of doxorubicin hydrochloride (0,1; 0,5 and 1,0μM), followed by the evaluation of proliferation and apoptosis after 12, 24 and 48 hours. Proliferation was evaluated by BrdU incorporation and it decreased at all time-points, with the most significant effects after 24 hours, when its rate dropped from 12,84±1,83% (n=4) to 2,41±0,27% (n=4, p
- Published
- 2008