Mahmoud M Kamel
Abstract
Introduction Doxorubicin (DOX) is one of the most potent anticancer agents, but its use is associated by development of cardiotoxicity that may lead to cardiomyopathy and congestive heart failure. Heart is sensitive to Reactive Oxidative Species (ROS) induced damage because of its highly oxidative metabolism and fewer antioxidant defences compared to other organs. Doxorubicin induces mitochondrial damage which causes continued production of free radicals and release of cytochrome c which induces apoptosis. Doxorubicin-induced cardiotoxicity is usually dose dependent . If the doxorubicin-induced cardiac complications prevented or at least reduced, higher doses could be utilized, thereby increasing cancer cure rates. The prevalence of glucose intolerance is increased in patients with malignancy especially those treated by DOX. Insulin resistance is correlated with increased risk for cancer. In addition, the rate of tumor recurrence, metastatic spread and fatal outcome is higher in cancer patients with hyperglycemia or type II diabetes. Metformin is an oral biguanide antihyperglycemic drug which can enhance insulin sensitivity. Metformin has been shown to have antioxidant properties and can decrease lipid peroxidation in various tissues. Noteworthy, Metformin significantly improved left ventricular function and survival in vivo murine model of heart failure, improves outcomes in patients with advanced systolic heart failure and may reduce the cardiovascular complications in diabetic patients. Sitagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor which improves hyperglycemia by inhibiting the inactivation of the incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide. The GLP-1 receptor is expressed in islet cells, kidney, lung, brain, the gastrointestinal tract and in the heart. The DPP-4 inhibitors caused decrease in the expression of myocardial fibrosis-related proteins and markers of cardiomyocyte stress in a rat model of uremic cardiomyopathy. This work aimed to compare the potential protective effect of the antihyperglycemic drugs; metformin and sitagliptin against doxorubicin-induced cardiotoxicity in male Wistar rats.