Cardiotoxicity is a serious complication of anticancer therapy by
anthracycline antibiotics. Except for intercalation into DNA/RNA structure, inhibition
of DNA-topoisomerase and histone eviction from chromatin, the main mechanism
of their action is iron-mediated formation of various forms of free radicals,
which leads to irreversible damage to cancer cells. The most serious adverse effect of
anthracyclines is, thus, cardiomyopathy leading to congestive heart failure, which is
caused by the same mechanisms. Here, we briefly summarize the basic types of free
radicals formed by anthracyclines and the main processes how to scavenge them.
From these, the main attention is paid to metallothioneins. These low-molecular cysteine-rich proteins are introduced and their functions and properties are reviewed.
Further, their role in detoxification of metals and drugs is discussed. Based on these beneficial roles,
their use as a new therapeutic agent against oxidative stress and for cardioprotection is critically evaluated
with respect to their ability to increase chemoresistance against some types of commonly used cytostatics.
Keywords: Anthracyclines, cardioprotection, cellular oxidative stress, chemoresistance, doxorubicin, free radicals, metallothionein.
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