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DOXORUBICIN: A CRITICAL REVIEW OF TOXICITY. Kaur Amandeep, Kaur Manpreet, Kumar Sunil, Sharma Ramica, Rana A. C.

DOXORUBICIN: A CRITICAL REVIEW OF TOXICITY.

Kaur Amandeep, Kaur Manpreet, Kumar Sunil, Sharma Ramica, Rana A. C.

International Journal of Natural Product Science 2012: Spl Issue 1:208.

Abstract(RBIP-208)

The anthracycline derivative doxorubicin (DXR) is a very potent drug with broad spectrum of biological activity. DXR is isolated from cultures of Streptomyces peucetius and is used in the management of various hematological malignancies and neo-plastic diseases such as leukemia, breast cancer and AIDS (acquired immune deficiency syndrome) related Kaposi’s sarcoma. The Clinical efficacy of drug in a wide range of malignant disorders is hampered by its dose limiting side effects such as cardiotoxicity, hepatotoxicity, nephrotoxicity and skin toxicity. The most serious long-term side effect of doxorubicin is cardiotoxicity, which can lead to dilated cardiomyopathy (DCM) and congestive heart failure (CHF).The most thoroughly examined hypothesis for doxorubicin-induced toxicity is based on the formation of reactive oxygen species (ROS), such as superoxide and hydrogen peroxide, by reactions catalyzed by the quinone moiety of doxorubicin. Further, membrane lipid per oxidation, mitochondrial damage, and iron-dependent oxidative damage to macromolecules, histamine release and disruption of calcium homeostasis are also implicated in the mechanism of drug related side effects. It was supposed that administration of a potent antioxidant and protective drug therapy together with a chemotherapeutic agent may be the proper advance to reduce the toxic side effects of drug. This review focuses briefly on DXR-induced side effects and the possible underlying mechanisms of drug related toxicity.

Key words: Doxorubicin, cardiotoxicity, hepatotoxicity, nephrotoxicity, necrosis and treatment.
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