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

Umesh B. Mahajan; Pradip D. Patil; Govind Chandrayan; Chandragouda R. Patil; Yogeeta O. Agrawal; Shreesh Ojha; Sameer N. Goyal

doi:10.1007/s11010-018-3276-1

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

Umesh B. Mahajan, Pradip D. Patil, Govind Chandrayan, Chandragouda R. Patil, Yogeeta O. Agrawal, Shreesh Ojha, Sameer N. Goyal

Department of Pharmacology

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	91-103
Number of pages	13
Journal	Molecular and cellular biochemistry
Volume	446
Issue number	1-2
DOIs	https://doi.org/10.1007/s11010-018-3276-1
Publication status	Published - Sept 1 2018

Keywords

Diabetes
Eplerenone
GSK-3β
Ischemia–reperfusion injury
PI3K/Akt pathway

ASJC Scopus subject areas

Molecular Biology
Clinical Biochemistry
Cell Biology

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10.1007/s11010-018-3276-1

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Mahajan, U. B., Patil, P. D., Chandrayan, G., Patil, C. R., Agrawal, Y. O., Ojha, S., & Goyal, S. N. (2018). Eplerenone pretreatment protects the myocardium against ischaemia/reperfusion injury through the phosphatidylinositol 3-kinase/Akt-dependent pathway in diabetic rats. Molecular and cellular biochemistry, 446(1-2), 91-103. https://doi.org/10.1007/s11010-018-3276-1

Eplerenone pretreatment protects the myocardium against ischaemia/reperfusion injury through the phosphatidylinositol 3-kinase/Akt-dependent pathway in diabetic rats. / Mahajan, Umesh B.; Patil, Pradip D.; Chandrayan, Govind et al.
In: Molecular and cellular biochemistry, Vol. 446, No. 1-2, 01.09.2018, p. 91-103.

Research output: Contribution to journal › Article › peer-review

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abstract = "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.",

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note = "Funding Information: Acknowledgements The authors gratefully acknowledge the financial support received under Early Career Research Award Scheme (File No. ECR/2016/001243) of Science and Engineering Research Board (SERB), Department of Science and Technology, New Delhi, India. The authors acknowledge the financial support for the research works in the laboratory of Dr. Shreesh Ojha from United Arab Emirates University, United Arab Emirates. Publisher Copyright: {\textcopyright} 2018, Springer Science+Business Media, LLC, part of Springer Nature.",

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AU - Chandrayan, Govind

AU - Patil, Chandragouda R.

AU - Agrawal, Yogeeta O.

AU - Ojha, Shreesh

AU - Goyal, Sameer N.

N1 - Funding Information: Acknowledgements The authors gratefully acknowledge the financial support received under Early Career Research Award Scheme (File No. ECR/2016/001243) of Science and Engineering Research Board (SERB), Department of Science and Technology, New Delhi, India. The authors acknowledge the financial support for the research works in the laboratory of Dr. Shreesh Ojha from United Arab Emirates University, United Arab Emirates. Publisher Copyright: © 2018, Springer Science+Business Media, LLC, part of Springer Nature.

PY - 2018/9/1

Y1 - 2018/9/1

N2 - 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.

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

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