الفهرس 
iNTRODUCTIONOnly 14 pages are availabe for public view
 |  | from | 76 |  |  |
| | | from | 76 | | |
Abstract
Myocardial infarction is defined as the irreversible death of the cardiomyocytes secondary to prolonged myocardial ischemia. After AMI, many inflammatory changes occur including altered levels of cytokines, changes in the numbers and activation states of various leukocyte populations, apoptosis and fibrosis. IL-1 is the major inflammatory cytokine mediating pro-inflammatory response.
The process of apoptosis was found to be present at the border of infarcted myocardium emphasizing its role in the pathogensis of MI. Casps are the main enzymes responsible for casp-mediated apoptosis. The later occurs either by extrinsic or intrinsic pathways which usually converge on a common effector casp, such as casp-3. Necrosis of the myocardium following MI can be assessed by cTn-I which is found to be the most specific in laboratory animals.
Rising evidence showed the potential cardiovascular benefits of oral anti-diabetic drugs as they possibly exert an anti-inflammatory effect regardless of their glucose-lowering action. In view of such a consideration, the present study was designed to assess the effect of metformin, sitagliptin and dapagliflozin on ECG changes, IL-1β, cTn-I, casp-3 in ISO induced MI rat model.
The present study was conducted on fifty male adult albino rats, which were divided into five groups including normal control group, ISO-induced MI control group and ISO-induced MI metformin, sitagliptin and dapagliflozin treated groups. ISO was administrated in a dose of 100 mg/kg SC in the last 2 days of the experiment. Metformin, sitagliptin and dapagliflozin were given, orally in a dose of 300 mg/kg/day, 10 mg/kg/day and 5 mg/kg/day for 14 days respectively.
Metformin, sitagliptin and dapagliflozin treated groups showed significant changes in ECG recordings, and lowering of serum levels of IL-1β, Casp-3 and cTn-I in comparison to ISO induced MI control group. Dapagliflozin treated rats had the lowest ST segment level and the highest R wave amplitude, slowest HR, longest R-R and shortest QT interval, lowest serum levels of IL-1β, Casp-3 and cTn-I compared to metformin and sitagliptin treated groups.
In conclusion, metformin, sitagliptin and dapagliflozin reduced the inflammation with subsequent reduction in apoptosis and necrosis in the myocardium. These was accompanied by improved ECG findings.