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myocytes to adriamycin and development of apoptosis has also coincided with the
activation of NF-kB pathway (Wang et a1.2002b). In cancer cells, the activation of NFkB
pathway after the treatment with adriamycin is found to cause the resistance to
apoptosis, while the activation of the same pathway in cardiac myocytes seems to be
involved in the activation of apoptosis.
The involvement of apoptosis in adriamycin induced cardiomyopathy and heart
failure was also examined in vivo. 'Wu et al. (2002) has reported the increased incidence
of apoptosis in both endothelial cells and cardiac myocytes in the hearts of the rats treated
with multiple injections of adriamycin for a period of two weeks (Wu et al. 2002). Study
by Kumar at al (2001) has followed the occurrence of apoptosis in different time points in
the hearts of the rats that were subjected to multiple treatments with adriamycin in a
cumulative dose of 15 mg/kg (Kumar et al. 2001). First signs of apoptosis were evident 4
days after the last dose of adriamycin, which was followed by a decline after 10 and 16
days after the treatment and peaked again at 2I days (Kumar et al. 2001). This biphasic
response in apoptosis may be attributed to the existence of lengthy post-treatment period
during which apoptosis is silent. The progression of adriamycin-induced cardiomyopathy
towards the end stage hart failure will, however, result in the re-activation of apoptotic
processes in cardiac myocytes.
I.g. Attempts for reducine cardiotoxicÍty
A number of attempts were made in finding the proper method which will provide the
adequate protection against adriamycin-induced cardiotoxicity. Any method that is
designed to minimize cardiotoxicity must not interfere with the adriamycin's
antineoplastic activity. This is considerably complicated due to the fact that the
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