| Doxorubicin (DOX) is an anthracycline antibiotic, it is one of the most effective and important anticancer agents widely used in the treatment of a variety of human cancers including acute leukaemia and malignant lymphoma as well as a number of solid tumor. However, cardiotoxicity greatly compromises the clinical application of DOX. In the past years, several mechanisms such as free radical hypothesis, calcium overload hypothesis, anthracycline metabolite hypothesis, histamine hypothesis have been proposed to account for DOX-induced cardiotoxicity. Among these, the free radical hypothesis is the most popular one that has been thoroughly investigated. DOX produces free radicals during its intracellular metabolism including hydroxide radical, superoxide anion and hydrogen peroxide. Endothelial nitric oxide synthase (eNOS) is the main enzyme mediating the metabolization of DOX, and is critically involved in DOX-induced apoptosis in cardiomyocytes. Among these free radicals, superoxide has been reported to be the major oxidant that mediates DOX toxicity. These highly toxic free radicals react with various intracellular components such as lipids, protein and DNA, resulting in oxidative damages which appear to play the major role in the development of cardiomyopathy. Generally, the most important protective mechanism for heart is the antioxidant defense system. However, oxidative injury occurs when excessive free radicals were generated that exceeded the protective capability of antioxidant defense system. Glutathione (GSH) is one of the main components of cardiac antioxidant defense system and plays important role in protection the heart against oxidative attacks.Metallothionein (MT) is low-molecular weight protein found in most tissues of a wide variety of vertebrate and invertebrate species, and characterized by their high... |
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