Possible Protective Mechanisms of Sitagliptin against Isoproternol Induced Myocardial Injury in Rat

Document Type : Original Article


Pharmacology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt


Sitaglebtin, dipeptidyl peptidase 4 inhibitors, has been investigated and proved to improve
triglycerides, low density lipoprotein and blood pressure, which are important risk factors for
cardiovascular diseases. Aim: The present study was designed to investigate the potential protective
effect of sitaglebtin in isoproterenol induced myocardial injury. Further assessment was done to
address the cardioprotective mechanism. Method: Male Wister rats were treated with sitaglebtin (30
mg/kg/day for 2 weeks by gavage) and/ or isoproterenol (85mg /kg; i.p. 24 hours apart at day 14th and
15th of the experiment). Results: Isoproternol induced a significant ECG changes, several pathological
changes and elevated cardiac enzymes. These changes were significantly attenuated by pre-treatment
of rats with sitaglebtin. As a marker of oxidative stress, isoproterenol caused significant decrease in
reduced glutathione level and superoxide dismutase with increase in malondialdhyde compared to the
control group. Sitaglebtin pretreatment restored these markers toward normal values. Energy decline
was assessed by measuring ATP/ADP, which decreased significantly in isoproterenol group and
significantly increased by sitaglebtin pretreatment. Isoproternol caused inflammatory effects indicated
by up-regulation of tumor necrosis factor-α expression in the myocardial tissue. Sitaglebtin also
counteracted inflammatory cell infiltration, other histopathological changes, and the overexpression
tumor necrosis factor-α in myocardial tissue. Collectively, these findings suggest that sitaglebtin, an
anti-diabetic agent, has cardioprotective effect against isoproterenol induced myocardial injury that
could be through antioxidant properties, TNF-α inhibition, and an enhancement of myocardial energy
state .