Abstract

POTENTIAL PROTECTIVE EFFECT OF SITAGLIPTIN AGAINST MYOCARDIAL INFARCTION IN RATS: MITIGATION OF OXIDATIVE STRESS AND INFLAMMATORY MEDIATORS

Amany. N. Ibrahim*, Amal MH. Mackawy

Abstract

Background Dipeptidyl peptidase-4 (DPP4) enzyme inhibition has been reported to increase plasma glucagon-like peptide-1 (GLP-1) level for controlling postprandial glucose concentration. DPP4 inhibitors have received attention for the potential of these interventions to positively impact on cardiovascular outcomes. The aim of the present study was to explore the potential protective effect of DPP-4 inhibitor on acute myocardial infarction induced experimentally in rats and possible mechanism of action. Material and methods Seventy two albino rats were divided randomly into 3 equal groups; normal control group rats were received physiological saline. Myocardial infarction groups pretreated with vehicle or sitagliptin (5mg/kg/day, orally by gastric gavage once a day) for 2 weeks before left coronary artery ligation for induction of acute myocardial infarction model in rats. Four hours after ligation of the left anterior descending coronary artery (LAD), the electrocardiogram, blood pressure, cardiac enzyme (CPK), myocardial tumor necrosis factor alpha (TNF-α), and lipid peroxidation as malondialdehyde level in the cardiac tissue were measured. Additionally, glutathione peroxidase and catalase were determined before and after myocardial infarction in all groups, in addition to histopathological examination. Results the induction of myocardial infarction resulted in highly peaked T wave in the ECG tracing, significant increase in serum CPK level, significant elevation of lipid peroxidation and TNF- α content of the myocardial tissue compared with control group. On the other hand, glutathione peroxidase and catalase were decreased. Pretreatment with sitagliptin (5mg/kg/day, orally) 2 weeks before ligation of LAD resulted in a significant decrease in peaked T wave, insignificant decrease of blood pressure, pronounced reduction in serum CPK level, reduction of myocardium lipid peroxidation and TNF-α content level in myocardial tissues. While, myocardial glutathione peroxidase and catalase contents were significantly increased. Histopathological changes were supported with biochemical changes. Conclusion the results highlight the efficacy of sitagliptin as cardioprotective drug against myocardial infarction by improving inflammatory status and oxidative stress.

Keywords: sitagliptin, oxidative stress, TNF-?, myocardial infarction, DPP-4 enzyme inhibitors.