Eplerenone pretreatment protects the myocardium against ischaemia/reperfusion injury through the phosphatidylinositol 3-kinase/Akt-dependent pathway in diabetic rats

• Published in: Molecular and cellular biochemistry Vol. 446; no. 1-2; pp. 91 - 103
• Main Authors: Mahajan, Umesh B., Patil, Pradip D., Chandrayan, Govind, Patil, Chandragouda R., Agrawal, Yogeeta O., Ojha, Shreesh, Goyal, Sameer N.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.09.2018; Springer; Springer Nature B.V
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Apoptosis; Biochemistry; Biomedical and Life Sciences; Blood pressure; Cardiology; Coronary artery; Diabetes; Diabetes mellitus; Heart; Heart diseases; Histology; Injury prevention; Ischemia; Life Sciences; Medical Biochemistry; Myocardium; Occlusion; Oncology; Oxidative stress; Phospholipids; Pretreatment; Proteins; Rats; Reperfusion; Rodents; Ventricle; Wortmannin; GSK-3β; Ischemia–reperfusion injury; PI3K/Akt pathway; Diabetes; Eplerenone
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-018-3276-1

We investigated the eplerenone-induced, PI3K/Akt- and GSK-3β-mediated cardioprotection against ischemia/reperfusion (I/R) injury in diabetic rats. The study groups comprising diabetic rats were treated for 14 days with 150 mg/kg/day eplerenone orally and 1 mg/kg wortmannin (PI3K/Akt antagonist) intraperitoneally with eplerenone. On the 15th day, the rats were exposed to I/R injury by 20-min occlusion of the left anterior descending coronary artery followed by 30 min of reperfusion. The hearts were processed for biochemical, molecular, and histological investigations. The I/R injury in diabetic rats inflicted a significant rise in the oxidative stress and apoptosis along with a decrease in the arterial and ventricular function and the expressions of PI3K/Akt and GSK-3β proteins. Eplerenone pretreatment reduced the arterial pressure, cardiac inotropy, and lusitropy. It significantly reduced apoptosis and cardiac injury markers. The histology revealed cardioprotection in eplerenone-treated rats. Eplerenone up-regulated the PI3K/Akt and reduced the GSK-3β expression. The group receiving wortmannin with eplerenone was deprived eplerenone-induced cardioprotection. Our results reveal the eplerenone-induced cardioprotection against I/R injury in diabetic rats and substantiate the involvement of PI3K/Akt and GSK-3β pathways in its efficacy.