Adv Pharm Bull. 2015;5(3):321-327.
doi: 10.15171/apb.2015.045
PMID: 26504753
PMCID: PMC4616890
Scopus id: 84983575308
  Abstract View: 355
  PDF Download: 171

Original Research

Involvement of Glycogen Synthase Kinase-3β and Oxidation Status in the Loss of Cardioprotection by Postconditioning in Chronic Diabetic Male Rats

Reza Badalzadeh 1, Mustafa Mohammadi 1 * , Bahman Yousefi 2, Safar Farajnia 3, Moslem Najafi 4, Shima Mohammadi 2

1 Department of Physiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
2 Students’ Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
3 Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
4 Department of Pharmacology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.


Purpose: Diabetes mellitus as a main risk-factor of ischemic heart disease may interfere with postconditioning’scardioprotective effects. This study aimed to investigate the involvement of glycogen synthase kinase-3β (GSK-3β) and oxidation status in chronic diabetes-induced loss of cardioprotective effect of ischemic-postconditioning (IPostC) in Wistar rats.

Methods: After 8 weeks of induction of diabetes by streptozotocin (50mg/kg), hearts of control and diabetic rats were isolated and mounted on a constant-pressure Langendorff system. All hearts were subjected to 30min regional ischemia followed by 60min reperfusion (by occluding and re-opening of left anterior descending coronary artery, respectively). IPostC was applied immediately at the onset of reperfusion. At the end of reperfusion, the infarct size of myocardium was measured via computerized planimetry. Myocardial contents of malondealdehyde and glutathione as indices of oxidative status were assayed spectrophotometrically and the total and phosphorylated forms of myocardial GSK-3β were quantified through western blotting.

Results: IPostC reduced the infarct size of control hearts from 41±2.9% to 28±1.9% (P<0.05), whereas it could not induce significant changes in infarct size of diabetic animals (35±1.8% vs. 39±3.1%). IPostC-induced reduction in malondealdehyde and elevation in glutathione contents were significant only in control not in diabetic hearts. The total forms of GSK-3β were similar in all groups; however, the phosphorylation of GSK-3β (at Ser9) by IPostC was greater in control hearts than diabetics (P<0.01).

Conclusion: The failure of cardioprotection by IPostC in diabetic hearts may be attributed to the loss of phosphorylation of GSK-3β and thereby increase in oxidative stress in diabetic states.

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