il\VOLVEMENT OF RETII\OIC ACID II{ - MSpace at the University of ...
il\VOLVEMENT OF RETII\OIC ACID II{ - MSpace at the University of ...
il\VOLVEMENT OF RETII\OIC ACID II{ - MSpace at the University of ...
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chronic toxic side effects <strong>of</strong> adriamycin (Siveski-Iliskovic et al. l995).Tre<strong>at</strong>ment with<br />
probucol significant improved hemodynamic functions and caused <strong>the</strong> decrease in<br />
overall mortality. Probucol also prevented <strong>the</strong> occurrence <strong>of</strong> ultrastructural changes in <strong>the</strong><br />
heart (Siveski-Iliskovic et al. 1995). Ano<strong>the</strong>r study using lymphoma bearing mice has<br />
shown th<strong>at</strong> protective effects <strong>of</strong> probucol did not interfere with antitumor effects <strong>of</strong><br />
adriamycin (Siveski-Iliskovic et al. 1995).<br />
The administr<strong>at</strong>ion <strong>of</strong> probucol also provides a protection against <strong>the</strong> adriamycininduced<br />
disturbances in <strong>the</strong> activity <strong>of</strong> <strong>the</strong> endogenous antioxidant reserve. Probucol<br />
administr<strong>at</strong>ion was shown to cause <strong>the</strong> depression in <strong>the</strong> SOD and GSHPs activity in <strong>the</strong><br />
hearts during <strong>the</strong> early stages <strong>of</strong> adriamycin-induced heart failure (Li et al. 2000; Li and<br />
Singal 2000). Probucol administr<strong>at</strong>ion was found maintain <strong>the</strong> GSHPx activity (Li et al.<br />
2000; Li and Singal 2000). Administr<strong>at</strong>ion <strong>of</strong> probucol was also shown to prevent a<br />
decrease in <strong>the</strong> MnSOD mRNA and protein levels <strong>at</strong> <strong>the</strong> l<strong>at</strong>e stages <strong>of</strong> adriamycininduced<br />
heart failure while increasing <strong>the</strong> SOD levels (Li et al. 2000; Li and Singal<br />
2000).<br />
One <strong>of</strong> <strong>the</strong> deleterious effects <strong>of</strong> adriamycin administr<strong>at</strong>ion is <strong>the</strong> increase in <strong>the</strong><br />
total lipid levels in plasma and myocardial tissue (Iliskovic and Singal 1997; Joles et al.<br />
1993). Due to its antilipdemic properties, probucol was shown to cause <strong>the</strong> normaliz<strong>at</strong>ion<br />
<strong>of</strong> plasma and myocardial triglyceride and cholesterol content (Iliskovic and Singal<br />
1997). One <strong>of</strong> <strong>the</strong> fe<strong>at</strong>ures <strong>of</strong> adriamycin-induced heart failure is a development <strong>of</strong><br />
cardiomyocyte apoptosis (Kumar et al. 1999). Probucol was found to cause significant<br />
decrease in <strong>the</strong> incidence adriamycin-induced apoptosis in <strong>the</strong> heart (Kumar et al.2001).<br />
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