Email this article Selegiline protects against isoproterenol-induced myocardial ischemia injury: a potential mechanistic role of the PI3K/AKT/mTOR signaling pathway
, Hosein Ataei-Goujani, Hossein Amini-Khoei, Maryam Anjomshoa, Somayeh Najafi-ChaleshtoriAbstract
Background and purpose: Selegiline, an irreversible monoamine oxidase B inhibitor, has been shown to have potential in reducing cell damage. The present study design focused on the cardioprotective effect of selegiline and its possible mechanism of action through phosphoinositide-3-kinase/serine-threonine kinase AKT/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway.
Experimental approach: Myocardial ischemia was induced in male Wistar rats by isoproterenol injection. Selegiline was administered (2 and 5 mg/kg) for 14 days. Electrocardiogram (ECG) parameters and serum markers were measured. PI3K, AKT, and mTOR protein expression and histopathological examination of cardiac tissue were performed. All data were analyzed using GraphPad Prism.
Findings/Results: Pre-treatment with selegiline (5 mg/kg) effectively restored ECG parameters changes and cardiac serum markers elevation seen in isoproterenol receiving groups, with a reduction of lactate dehydrogenase by 55.2% and creatine kinase-myoglobin bind level by 80.1%. Histopathological examination of cardiac tissue revealed successful prevention of fibrosis and inflammation following isoproterenol administration in selegiline-treated groups. Furthermore, western blot analysis demonstrated that pre-treatment with selegiline (5 mg/kg) increased the proportion of phosphorylated to non-phosphorylated proteins involved in the PI3K/AKT/mTOR signaling pathway.
Conclusions and implications: Selegiline administration could protect against myocardial ischemia, induced following isoproterenol injection, which is mediated through PI3K/AKT/mTOR signaling pathways. However, future study needs to focus more on the exact protective route of selegiline action.
Keywords: Cardiovascular Diseases; Isoproterenol; Monoamine oxidase inhibitor; Myocardial ischemia; Selegiline.
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