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characteized by a significant decrease in the CRABP II expression which was prevented
by probucol suggesting the restoration of retinoic acid metabolism as well as signaling.
YII. Bax and Bcl-xl exPression
Most important proteins, involved in the regulation of apoptosis, are Bax and Bclxl
(Adams and Cory 1998; Huang et al. 1998). Increased expression of Bax protein leads
to changes in the mitochondrial membrane transition potential, thereby resulting in the
leakage of cytochrome C from mitochondria to cytosol, leading to the activation of downstream
caspases and thus apoptosis (Desagher and Martinou 2000; Shimizu et al. 2000)'
In contrast, an increased expression of anti-apoptotic protein Bcl-xl results in the
stabilization of mitochondrial membrane potential thus preventing cytochrome C release
and apoptosis (Hu et al. 1998; Huang and Chou 1998). ln this study the development of
adriamycin-induced cardiomyopathy was accompanied by a significant increase in the
expression of Bax and a significant decrease in Bcl-xl proteins resulting in a significant
increase in the Bax/Bcl-xl ratio. These data are complemented by the in vitro studies as
well, where adriamycin resulted in a significant increase in Bax and a decrease in the Bclxl
levels. These changes also reflected as in increase in the BaxlBcl-xl ratio, which was
associated with an increase apoptosis.
The administration of probucol to the adriamycin gtoup animals resulted in a
significant decrease in Bax, a significant increase in the Bcl-xl levels and a significant
decrease in the BaxlBcl-xl ratio. Since probucol is shown to protect against adriamycininduced
heart failure, this protection, at least in part, may be due to the prevention of
adriamycin-induced apoptosis in cardiac myocytes. Antioxidant trolox in isolated cardiac
myocytes also modulated adriamycin-induced increase in Bax and decrease in Bcl-xl
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