Abstract 15445: The Sirtuin SIRT3 Blocks Doxorubicin-induced Cardiac Hypertrophic Response of Mice

Background and objective: Doxorubicin is a chemotherapeutic drug widely used to treat variety of cancers. One of the serious side effects of doxorubicin is its toxicity to the heart. Previously, we have shown that overexpression of SIRT3 blocks the hypertrophic response of the heart to agonist treatments. This study was undertaken to investigate whether SIRT3 can also attenuate the doxorubicin-induced cardiac hypertrophic response in mice. Methods and results: Neonatal rat cardiomyocytes overexpressed with SIRT3 and treated with doxorubicin (10μM) showed 28% reduced mean fluorescent intensity for CM-H2DCFDA dye, compared to mock infected control cells treated with doxorubicin, thus suggesting that SIRT3 was capable of blocking doxorubicin-induced ROS synthesis in cardiomyocytes. To examine the cardioprotective effects of SIRT3 in doxorubicin-induced cardiotoxicity in vivo; we used a cumulative dose of 15mg/kg of doxorubicin for two different time points. One group of mice was treated intraperitoneally wit...