Download Anthracycline Chemistry and Biology II: Mode of Action, by Giovanni Luca Beretta, Franco Zunino (auth.), Karsten Krohn PDF

By Giovanni Luca Beretta, Franco Zunino (auth.), Karsten Krohn (eds.)

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Extra resources for Anthracycline Chemistry and Biology II: Mode of Action, Clinical Aspects and New Drugs

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A One-electron quinone reduction; B Two-electron side chain carbonyl reduction; C One electron hydroquinone oxidation. 2 Two-Electron Reductive Bioactivation Anthracyclines are said to gain toxicity also after a two-electron reduction of the side chain C-13 carbonyl moiety. In laboratory animals such reaction is mediated by heterogeneous families of cytoplasmic NADPHdependent aldo/keto- or carbonyl-reductases, but in human myocardial samples it seems to be mediated almost exclusively by a specific family of aldehyde reductases [26, 27].

Menna et al. the summation of injuries inflicted by de novo DOX and long-lived cardiac residues of prior DOX. Retrospective clinical studies have also shown that the severity of cardiac damage in a given patient is inversely correlated to the levels of P glycoprotein (Pgp) in the endothelium of arterioles and capillaries of the heart of that patient [5]. Pgp is a prominent member of the superfamily of ATPbinding proteins that extrude anthracyclines and many other drugs from within the cells into the extracellular fluids.

One-Electron Oxidative Degradation and Detoxification . . . . . . . . . . . . . . . . . . . . . . 4 Translating the Metabolic Determinants of Cardiotoxicity into Protective Strategies Antioxidants . . . . . . . . . Iron Chelators . . . . . . . . Noncardiotoxic Anthracycline Analogs . Modulators of Anthracycline Degradation . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Cardiotoxic Synergism of Anthracyclines with Other Drugs .

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