Eplerenone Attenuates Myocardial Infarction in Diabetic Rats via Modulation of the PI3K-Akt Pathway and Phosphorylation of GSK-3β

Am J Transl Res. 2018 Sep 15;10(9):2810-2821. eCollection 2018.

Abstract

We investigated the effect of eplerenone on myocardial infarcted diabetic rats via modulation of the PI3K/Akt pathway and its downstream target GSK-3β. Diabetes was induced by administration of a single dose of streptozotocin (55 mg/kg IP). Diabetic rats received either eplerenone or PI3k/Akt antagonist (wortmannin) or in combination for 14 days with concurrent administration of isoproterenol (100 mg/kg s.c) on 13th and 14th day. Isoproterenol prompted cardiotoxicity and was demonstrated by a decrease in the maximal positive rate of developed left ventricular pressure, the maximal negative rate of developed left ventricular pressure and an increase in left ventricular end-diastolic pressure along with oxidative stress. Myocardial infarcted diabetic rats exhibited increased myonecrosis, edema, and apoptotic cell death. Treatment with eplerenone significantly improved the redox status of the myocardium. Eplerenone markedly inhibited Bax expression, TUNEL-positive cells, and myonecrosis. On the other hand, the administration of eplerenone and wortmanin did not draw out the same effects, when administered concomitantly or individually. Moreover, the rats treated with eplerenone showed increased expression of PI3K/Akt and decreased its downstream target GSK-3β. The present study confirms the protective effects of eplerenone on myocardial infarction in diabetic rats via modulation of PI3K/Akt pathway and its downstream regulator GSK-3β.

Keywords: ISO; PI3K/Akt/GSK-3β; STZ; diabetes; eplerenone.