Thesis (M.Sc.) - Cairo University - Faculty of Medicine - Department of Pharmacology

Background and aim: Cardiotoxicity is the most important adverse effect of doxorubicin. Cancer patients especially who are treated with doxorubicin are more prone to develop hyperglycemia. The present study was designed to investigate the effect of the two well known anti-hyperglycemic drugs; metformin and sitagliptin, in the prevention of doxorubicin-induced cardiotoxicity in rats. Methods: Male wistar rats weighing 200-250 g were allocated in the following six groups; three control groups, the negative control group (Group 1) in which the rats were injected with normal saline intraperitoneally for 15 injections over 3 weeks, metformin and sitagliptin control groups in which the rats were treated daily for 3 weeks with either metformin 150 mg/kg orally (Group 2), or sitagliptin 10 mg/kg orally (Group 3). Three doxorubicin-induced cardiotoxicity groups; doxorubicin group, rats were injected intraperitoneally with a cumulative dose of 15 mg/kg of doxorubicin for 3 weeks for induction of cardiotoxicity (Group 4). Metformin and sitagliptin treated groups; in which the rats were injected with doxorubicin as in group 4 and treated daily for 3 weeks with either metformin (Group 5) or sitagliptin (Group 6) orally in the same previously mentioned doses. The following parameters were assessed; mean body weight, systolic blood pressure, electrocardiographic (ECG) changes, serum lactate dehydrogenase (LDH) serum creatine kinase-myocardium band (CK-MB), serum glucose and cardiac malondialdhyde (MDA) level. In-vitro study was performed on the isolated rats{u2019} hearts to test the cardiac contractility in response to isoprenaline in all studied groups. In addition, the heart/body weight (HW/BW) ratio was measeured and histopathological examination of the isolated hearts{u2019} tissues was performed

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