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INTRODUCTION
Adriamycin, an anthracycline drug, has been widety used in the treatment of
various human malignancies. Its wider clinical usage is limited by the development of
dose dependent cardiotoxicity which generally progresses into refractory heart failure.
The development of cardiotoxicity could be concurrent with the therapy or it may have a
late onset. Development of cardiomyopathy and congestive heart failure are dosedependant.
Adriamycin-induced heart failure is accompanied by myofibriliar loss, dilatation
of sarcoplasmic reticulum, swelling of mitochondria and increase in lysosomes. Cardiac
cell loss is achieved through drug-induced necrosis and apoptosis. Apoptotic cell-loss is
supported by the fact that the adriamycin administration resulted in the release of
cytochrome C from mitochondria and caused an increased expression of different
apoptotic markers in cardiac cells. Although the cause of adriamycin-induced
cardiotoxicity is multifactorial, the most prominent factor in its pathogenesis is increased
oxidative stress. The increased production of free radicals is mainly due to the
anthraquinone moiety in the adriamycin molecule which cycles between its quinone and
semiquinone form thus releasing electrons. These free electrons captured by oxygen can
lead to the production of free-radicals which can interfere with the normal cell
physiology. The increase in oxygen free radical production and a decrease in endogenous
antioxidants results in the oxidative stress. Such an increase in the oxidative stress has
also been shown to cause apoptosis in cardiac myocytes. The usage of antioxidants was
shown to result in the protection against adriamycin-induced apoptosis which further
supports the involvement of oxidative stress and apoptosis in the pathogenesis of