Current knowledge about adriamycin cardiomyopathy indicates that the major cause of this condition is increased oxidative stress although the drug's antitumor action in patients may involve other mechanisms. Controversies about the different antioxidants in preventing cardiomyopathy likely stem from the fact that antioxidants must be effective in both the lipid and water phases, and the dose must be optimal, in order to be protective. Probucol, an antioxidant and promoter of endogenous antioxidants, is one such agent. Conducting clinical trials with an optimal dose of probucol is the next step and should make this great anticancer drug safer and more efficient in the fight against the cancer.
Although researchers in radiation and cancer biology have known about the existence of free radicals and their potential role in pathobiology for several decades, cardiac biologists only began to take notice of these noxious species in the 1970s. Exponential growth of free radical research occurred after the discovery of superoxide dismutase in 1969. This antioxidant enzyme is responsible for the dismutation of superoxide radical -a free radical chain initiator. A fine balance between free radicals and a variety of endogenous antioxidants is believed to exist. Any disturbance in this equilibrium in favour of free radicals causes an increase in oxidative stress and initiates subcellular changes leading to cardiomyopathy and heart failure. Our knowledge about the role of free radicals in the pathogenesis of cardiac dysfunction is fast approaching the point where newer therapies employing antioxidants are in sight.
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