Introduction
Doxorubicin, an anthracycline antibiotic, is commonly used as an effective antineoplastic agent, in the treatment of various of malignancies, including leukemia, lymphoma, and solid tumors. Unfortunately, the clinical use of this drug is limited by cumulative dose-dependent cardiotoxicity, which may cause irreversible and severe effect of cardiomyopathy [1]
The specific mechanisms of doxorubicin (DOX) induced cardiotoxicity are complex and although decades of research on this drug, remain unclear. Different mechanisms may play a role in the effects induced by DOX, including suppression of protein synthesis and nucleic acid formation, lysosomal deformities, changes in adrenergic function, mitochondrial abnormalities , changed sarcolemmal Ca2+ transport, calcium …show more content…
Molecular oxygen is reduced to superoxide anion (O−2·) that is converted to other forms of reactive oxygen species. ROS reacts with lipid, protein and other cellular components to cause damage to cell membrane and mitochondria of the heart muscle fibers [1]
These free radicals may then cause injury to the heart, an organ that has a relatively low level of antioxidant enzymes such as superoxide dismutase (SOD) and catalase. Others studies propose that the mechanism of DOX-induced heart apoptosis is dependent on the activation of tumor suppressor p53 [9] [10].
Melatonin (MEL), is the chief secretory product of the pineal gland of all mammals. During the day the pineal gland is inactive, when the sun goes down and darkness occurs, the pineal gland is activated and starts to actively produce melatonin. MEL participates in circadian rhythm regulation and plays an important role in anti aging processes [11]
Doxorubicin, an anthracycline antibiotic, is commonly used as an effective antineoplastic agent, in the treatment of various of malignancies, including leukemia, lymphoma, and solid tumors. Unfortunately, the clinical use of this drug is limited by cumulative dose-dependent cardiotoxicity, which may cause irreversible and severe effect of cardiomyopathy [1]
The specific mechanisms of doxorubicin (DOX) induced cardiotoxicity are complex and although decades of research on this drug, remain unclear. Different mechanisms may play a role in the effects induced by DOX, including suppression of protein synthesis and nucleic acid formation, lysosomal deformities, changes in adrenergic function, mitochondrial abnormalities , changed sarcolemmal Ca2+ transport, calcium …show more content…
Molecular oxygen is reduced to superoxide anion (O−2·) that is converted to other forms of reactive oxygen species. ROS reacts with lipid, protein and other cellular components to cause damage to cell membrane and mitochondria of the heart muscle fibers [1]
These free radicals may then cause injury to the heart, an organ that has a relatively low level of antioxidant enzymes such as superoxide dismutase (SOD) and catalase. Others studies propose that the mechanism of DOX-induced heart apoptosis is dependent on the activation of tumor suppressor p53 [9] [10].
Melatonin (MEL), is the chief secretory product of the pineal gland of all mammals. During the day the pineal gland is inactive, when the sun goes down and darkness occurs, the pineal gland is activated and starts to actively produce melatonin. MEL participates in circadian rhythm regulation and plays an important role in anti aging processes [11]