Combined postconditioning with ischemia and cyclosporine-A restore oxidative stress and histopathological changes in reperfusion injury of diabetic myocardium

Document Type: Original Article


1 Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

2 Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

3 Cardiovascular Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

4 Department of Physiology, Tabriz Branch, Islamic Azad University, Tabriz, Iran

5 Department of Pathology, Tabriz Branch, Islamic Azad University, Tabriz, Iran


Objective(s): Chronic diabetes impedes cardioprotection in reperfusion injury and hence protecting the diabetic heart would have important outcomes. In this study, we evaluated whether combined postconditioning with ischemia and cyclosporine-A can restore oxidative stress and histopathological changes in reperfusion injury of the diabetic myocardium.
Materials and Methods: Streptozocin-induced diabetic rats’ hearts and nondiabetic controls in eight subgroups (with or without receiving ischemic-postconditioning (IPostC), cyclosporine-A, an inhibitor of mitochondrial permeability transition, or both of them) suffered from 30 min regional ischemia followed by 45 min reperfusion on an isolated-heart Langendorff system. The levels of lactate dehydrogenase (LDH) in the coronary effluent, and the levels of oxidative stress markers including 8-isoprostane, superoxide dismutase (SOD), glutathione peroxidase (GPX), and total antioxidant capacity (TAC) in myocardial supernatant prepared from the ischemic zone were measured using specific kits, spectrophotometrically. Histopathological studies were performed through the hematoxylin-eosin staining method.
Results: Administration of IPostC and cyclosporine-A (alone or together) in nondiabetic hearts potentially reduced the severity of histological changes and level of LDH release as compared with untreated-controls (P<0.05). Administration of any lone procedures in diabetic hearts did not show significant cardioprotective effects (P>0.1). However, the combined postconditioning with ischemia and CsA exerted significant protective effects in diabetic hearts (P<0.05).
Conclusion: By augmenting the protective effects of IPostC and CsA through their combined application, reperfusion injury and related oxidative stress are reduced in diabetic hearts similar to non-diabetics.


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