il\VOLVEMENT OF RETII\OIC ACID II{ - MSpace at the University of ...

The usage of Probucol.' Most promising results in the protection against adriamycininduced
cardiomyopathy were produced by the usage of the drug Probucol. Probucol,
4,4'-(isopropyldendithio)-bis-(2,6-diterbuthyl-phenol),
was first time introduced in the
early 70's as cholesterol lowering agent (Fig. 3) (Barnhart et al. 1970). The usage of
probucol was soon shadowed by the fact that that this lipid lowering drug did not only
lower plasma low density lipoproteins (LDL) but it also caused a significant decrease in
the high density lipoprotein fraction (HDL) (Zimetbaum et al. 1990). Another significant
characteristic of probucol is that it acts as an antioxidant preventing the occurrence of
atherosclerosis by inhibiting the oxidation of LDL (Steinberg et al. 1988). The usage of
probucol was shown to result in the regression of atherosclerotic lesions in a primate
model (Wissler and Vesselinovitch 1983). The administration of probucol was also found
to prevent the increase in a lipid peroxide levels in animals treated with adriamycin
(Iliskovic et al.1999; Li et al. 2000; Li and Singal 2000).
c(cH3)3
CH"
c(cH3)3
SS
I
c(cH3)3
I
CH"
c(cH3)3
Figure 3: Chemical structure of probucol
Siveski-Iliskovic et al. (1995) has reported that pre and concurrent treatment with
I20 mglkg of probucol resulted in the prevention of the development of acute and
2t