Possible Protective Mechanisms of Sitagliptin against Isoproternol Induced Myocardial Injury in Rat | ||||
| Ain Shams Journal of Forensic Medicine and Clinical Toxicology | ||||
| Article 2, Volume 24, Issue 1, January 2015, Page 11-20 PDF (542.37 K) | ||||
| Document Type: Original Article | ||||
| DOI: 10.21608/ajfm.2015.18653 | ||||
 View on SCiNiTO | ||||
| Author | ||||
| Wesam El-Bakly | ||||
| Pharmacology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt | ||||
| Abstract | ||||
| 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 . | ||||
| Keywords | ||||
| Isoproternol (ISO); Sitagliptin (SL); ATP/ADP, oxidative stress; myocardium | ||||
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