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Pharmacological cardioprotection with iron chelators and anthracycline cardiotoxicity
Popelová, Olga ; Geršl, Vladimír (advisor) ; Fusek, Josef (referee) ; Kolář, František (referee)
In this Ph.D. thesis, following aims were addressed: 1) potentially cardioprotective effects of deferiprone on the model of daunorubicin-induced chronic cardiotoxicity in rabbits, 2) the role of apoptotic cell death in the development of anthracycline cardiotoxicity, 3) cardioprotective effects of dexrazoxane against chronic anthracycline cardiotoxicity with a focus on rescue of cardiac myocytes from programmed cell death and oxidative stress, and 4) staging of myocardial changes in the time-course of chronic anthracycline cardiotoxicity development. First, using the leukemic cell line, deferiprone (1-300 µmol/L) was shown not to blunt the antiproliferative effect of daunorubicin. Instead, at higher concentrations of deferiprone, the augmentation of antiproliferative actions of both agents was observed. However, in the cardioprotective study deferiprone failed to afford significant protection against daunorubicin-induced mortality, cardiac dysfunction, morphological cardiac deteriorations, plasma cardiac troponin T rise as well as myocardial lipoperoxidation. This finding contrasted with previous positive outcomes of in vitro studies. Hence, this study changes the current view on deferiprone as a potential cardioprotectant against anthracycline cardiotoxicity. In addition, these results, together...
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Pharmacological cardioprotection with iron chelators and anthracycline cardiotoxicity
Popelová, Olga ; Geršl, Vladimír (advisor) ; Fusek, Josef (referee) ; Kolář, František (referee)
In this Ph.D. thesis, following aims were addressed: 1) potentially cardioprotective effects of deferiprone on the model of daunorubicin-induced chronic cardiotoxicity in rabbits, 2) the role of apoptotic cell death in the development of anthracycline cardiotoxicity, 3) cardioprotective effects of dexrazoxane against chronic anthracycline cardiotoxicity with a focus on rescue of cardiac myocytes from programmed cell death and oxidative stress, and 4) staging of myocardial changes in the time-course of chronic anthracycline cardiotoxicity development. First, using the leukemic cell line, deferiprone (1-300 µmol/L) was shown not to blunt the antiproliferative effect of daunorubicin. Instead, at higher concentrations of deferiprone, the augmentation of antiproliferative actions of both agents was observed. However, in the cardioprotective study deferiprone failed to afford significant protection against daunorubicin-induced mortality, cardiac dysfunction, morphological cardiac deteriorations, plasma cardiac troponin T rise as well as myocardial lipoperoxidation. This finding contrasted with previous positive outcomes of in vitro studies. Hence, this study changes the current view on deferiprone as a potential cardioprotectant against anthracycline cardiotoxicity. In addition, these results, together...
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Pharmacological cardioprotection with iron chelators and anthracycline cardiotoxicity
Popelová, Olga ; Geršl, Vladimír (advisor) ; Fusek, Josef (referee) ; Kolář, František (referee)
In this Ph.D. thesis, following aims were addressed: 1) potentially cardioprotective effects of deferiprone on the model of daunorubicin-induced chronic cardiotoxicity in rabbits, 2) the role of apoptotic cell death in the development of anthracycline cardiotoxicity, 3) cardioprotective effects of dexrazoxane against chronic anthracycline cardiotoxicity with a focus on rescue of cardiac myocytes from programmed cell death and oxidative stress, and 4) staging of myocardial changes in the time-course of chronic anthracycline cardiotoxicity development. First, using the leukemic cell line, deferiprone (1-300 µmol/L) was shown not to blunt the antiproliferative effect of daunorubicin. Instead, at higher concentrations of deferiprone, the augmentation of antiproliferative actions of both agents was observed. However, in the cardioprotective study deferiprone failed to afford significant protection against daunorubicin-induced mortality, cardiac dysfunction, morphological cardiac deteriorations, plasma cardiac troponin T rise as well as myocardial lipoperoxidation. This finding contrasted with previous positive outcomes of in vitro studies. Hence, this study changes the current view on deferiprone as a potential cardioprotectant against anthracycline cardiotoxicity. In addition, these results, together...
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