Diabetic cancer patients treated with Doxorubicin (DOX), a potent chemotherapeutic drug induces cardiac toxicity. However, molecular mechanisms of cardiac toxicity in this specific disease progression in patients and animal models are completely unknown. Therefore, we designed a study to understand the effects of doxorubicin induced cardiac toxicity in diabetic animals and involved pathophysiological mechanisms. C57BL/6J mice were divided into DOX and diabetic (STZ) treated four groups; control, STZ, DOX and DOX+STZ. At Day 14, animals were sacrificed, echocardiography was used to examine heart function, heart and blood samples were collected to investigate apoptotic mechanisms (Caspase 3, BAX, Bcl2), inflammation and cardiac remodeling. Our data shows a significant (p<0.05) increase in glucose levels, apoptotic markers, monocyte infiltration at the site of apoptosis and triggered inflammatory immune response (TNF-α and IL-6), in DOX+STZ animals compared to control and experimental groups. We also observed significant (p<0.05) increase in myofibrillar area, fibrosis and significantly decreased (p<0.05) cardiac function in DOX-treated diabetic animals compared with controls. In conclusion, our data suggest that DOX-induces significantly increased apoptosis, fibrosis and structural alterations in diabetic hearts compared to non-diabetic animals.

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