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PHARMASPIRE - Volume 11, Issue 2, April - June, 2019

Pages: 51-62

Date of Publication: 14-Jun-2022

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Role of phosphoinositide-3-kinase/AKT activation mediated by inhibition of protein tyrosine phosphate-1B inhibitor in cardioprotection

Author: Shivani Verma, Himanshi Khera, Anupam Awasthi, Sidharth Mehan

Category: Pharmaceutics


Background: Dyslipidemia is a downregulator of phosphoinositide-3-kinase (PI3K)/AKT-mediated cell survival pathway and reduces the preconditioning potential in ischemic-reperfusion (I/R) injured rat heart ultimately leads to cardiac cell death. Objective: The present study was designed to explore and confirm the pharmacological perspective of sodium orthovanadate (SOV), an inhibitor of tyrosine phosphate-1B protein against ischemic-reperfusion (I/R) injury in dyslipidemic rat. Martials and Methods: The dyslipidemic rodent hearts were isolated and fixed on Langendorff’s device, exposed to 30 miniature reperfusion. Ischemic preconditioning was started by four episodes of 5 min ischemia and 5 min reperfusion. Infarction was assessed using triphenyltetrazolium chloride staining, and coronary effluent was inspected for lactate dehydrogenase (LDH) and creatinine kinase-MB discharge to decide the degree of myocardial damage. The cardiac discharge of nitric oxide (NO) was assessed by determining the discharge of nitrite in coronary emission. Results: Pharmacological preconditioning with SOV significantly re-imposed I/R mediated myocardial infarction in dyslipidemic rat heart when compared with dyslipidemic and I/R control group. In this study, the statistical data show the significant values P < 0.05. However, in observed results, cardioprotection was abolished by perfusion of BEZ-235, a PI3K/AKT pathway inhibitor noted in terms of myocardial injury events such as a rise in myocardial infarct mass, tumor necrosis factor-alpha, LDH, CK-MB, and also decrease in the release of NO. Conclusion: Hence, it stated that SOV repairs impaired cardioprotective effect in dyslipidemic rat heart maybe because of activation of the PI3K/AKT cell survival pathway which was confirmed using PI3K/AKT inhibitor BEZ-235.

Keywords: Dyslipidemia, ischemic reperfusion injury, ischemic preconditioning, phosphoinositide-3-kinase, protein kinase-B


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