title: Chronic type-I diabetes could not impede the anti-inflammatory and anti-apoptotic effects of combined postconditioning with ischemia and cyclosporine A in myocardial reperfusion injury.
abstract: It has been shown that diabetes modifies the myocardial responses to ischemia/reperfusion (I/R) and to cardioprotective agents. In this study, we aimed to investigate the effects of combined treatment with ischemic postconditioning (IPostC) and cyclosporine A (CsA) on inflammation and apoptosis of the diabetic myocardium injured by I/R. Eight weeks after induction of diabetes in Wistar rats, hearts were mounted on a Langendorff apparatus and were subsequently subjected to a 30-min regional ischemia followed by 45-min reperfusion. IPostC was induced at the onset of reperfusion, by 3 cycles of 30-s reperfusion/ischemia (R/I). The concentration of creatine kinase (CK), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 were determined; the levels of total and phosphorylated glycogen synthase kinase 3 beta (p-GSK3β) and B-cell lymphoma 2 (Bcl-2) were quantified by western blotting, and the rate of apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining. Administration of either IPostC or CsA alone in nondiabetic animals significantly reduced CK, TNF-α, IL-1β, and IL-6 concentrations, increased the p-GSK3β and Bcl-2, and decreased the level of apoptosis (P < 0.05) but had no effect on diabetic hearts. However, in diabetic animals, after administration of CsA, the cardioprotective effects of IPostC in increasing the p-GSK3β and Bcl-2 and decreasing apoptosis and inflammation were restored in comparison with nonpostconditioned diabetic hearts. IPostC or CsA failed to affect apoptosis and inflammation and failed to protect the diabetic myocardium against I/R injury. However, combined administration of IPostC and CsA at reperfusion can protect the diabetic myocardium by decreasing the inflammatory response and apoptosis.
authors: Cardiovascular Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.|Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.|Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors: Reza
authors: R
authors: Badalzadeh
authors: Department of Basic Sciences, Maragheh University of Medical Sciences, Maragheh, Iran.
authors: Ako
authors: A
authors: Azimi
authors: Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors: Alireza
authors: A
authors: Alihemmati
authors: Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. yousefib@tbzmed.ac.ir.|Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. yousefib@tbzmed.ac.ir.
authors: Bahman
authors: B
authors: Yousefi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D003131:Combined Modality Therapy; D003331:Coronary Vessels / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D016572:Cyclosporine / Q000627:therapeutic use*; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced / Q000150:complications*; D058065:Diabetic Cardiomyopathies / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D066298:In Vitro Techniques; D057775:Ischemic Postconditioning; D008297:Male; D009203:Myocardial Infarction / Q000150:complications / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D011897:Random Allocation; D017208:Rats, Wistar; D013311:Streptozocin / Q000633:toxicity
chemical_list: D015415:Biomarkers; D016207:Cytokines; D007166:Immunosuppressive Agents; D013311:Streptozocin; D016572:Cyclosporine
keywords: Apoptosis; Cyclosporine A; Diabetes; Inflammation; Myocardial reperfusion injury; Postconditioning