Suppression of Doxorubicin and Hypoxia Induced Mitochondrial Perturbations and Necrotic Cell Death of Ventricular Myocytes by the Polyphenolic Compound Ellagic Acid

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dc.contributor.authorAfsharinezhad, Pegah
dc.date.accessioned2018-07-10T16:36:50Z
dc.date.available2018-07-10T16:36:50Z
dc.date.issued2016
dc.date.submitted2018-07-10T16:36:50Zen
dc.description.abstractEllagic acid (EA), is a polyphenolic compound with strong antioxidant properties, however, the effects of EA on cardiac cell death have not been formally investigated. In this report, we provide new exciting evidence that EA suppressed mitochondrial perturbations and cell death of cardiac myocytes mediated by the chemotherapy drug doxorubicin (Dox) or hypoxia (HPX). Cells treated with Dox or subjected to HPX exhibited a marked increase in the inducible death protein Bcl-2 Nineteen Kilodalton Interacting protein 3 (Bnip3). This coincided with mitochondrial perturbations including increased reactive oxygen species (ROS), loss of mitochondrial membrane potential, increased mitochondrial fission and reduced cell viability compared to vehicle treated normoxic control cells. Importantly cardiac myocytes treated with Dox in the presence of EA were indistinguishable from vehicle treated control cells displaying normal mitochondrial morphology, reduced ROS, and preserved mitochondrial membrane potential. Interestingly, mitochondrial targeting of Bnip3 in cells treated with Dox was markedly decreased by EA. This was accompanied by a concomitant reduction in cardiac cell death and increased cell viability. Hence, the present findings provide the first direct evidence that EA is sufficient to suppress mitochondrial injury and cell death of cardiac myocytes induced by Dox and hypoxia by a mechanism that impinges upon the death protein Bnip3. Our exciting data further suggest that by mitigating the cardiotoxic effects of Dox, adjunctive therapy with EA may provide a therapeutic advantage to cancer patients undergoing anthracycline treatment.en_US
dc.identifier.urihttp://hdl.handle.net/1993/33091
dc.rightsopen accessen_US
dc.subjectellagic aciden_US
dc.titleSuppression of Doxorubicin and Hypoxia Induced Mitochondrial Perturbations and Necrotic Cell Death of Ventricular Myocytes by the Polyphenolic Compound Ellagic Aciden_US
dc.typebachelor thesisen_US
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