Abstract
Insulin resistance increases risk of cardiovascular diseases. This work investigated the protective effect of pioglitazone on myocardial infarction (MI) in non-diabetic and diabetic rats, focusing on its role on advanced glycated endproducts (AGEs) and cardiac apoptotic machinery. Male rats were divided into 2 experiments: experiment I and II (non-diabetic and diabetic rats) were assigned as saline, MI (isoproterenol, 85 mg/kg, daily), and MI+pioglitazone (5, 10, and 20 mg/kg). Injection of isoproterenol in diabetic rats produced greater ECG disturbances compared to non-diabetic rats. Treatment with pioglitazone (5 mg/kg) reduced the infarct size and improved some ECG findings. Pioglitazone (10 mg/kg) enhanced ECG findings, improved the histopathological picture and downregulated apoptosis in cardiac tissues. Whereas the higher dose of pioglitazone (20 mg/kg) did not improve most of the measured parameters but rather worsened some of them, such as proapoptotic markers. Importantly, a positive correlation was found between serum AGEs and cardiac AGE receptors (RAGEs) versus caspase 3 expression in the two experiments. Therefore, the current effect of pioglitazone was, at least in part, mediated through downregulation of AGE-RAGE axis and inhibition of apoptosis. Consequently, these data suggest that pioglitazone, at optimized doses, may have utility in protection from acute MI.
Keywords:
advanced glycated end products; apoptose; apoptosis; infarctus du myocarde; myocardial infarction; pioglitazone; produits terminaux de glycation; rat.
MeSH terms
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Adrenergic beta-Agonists / poisoning
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Animals
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Apoptosis / drug effects*
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Cardiotonic Agents / administration & dosage
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Cardiotonic Agents / adverse effects
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Cardiotonic Agents / therapeutic use*
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Diabetes Mellitus, Type 2 / complications
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Diabetes Mellitus, Type 2 / drug therapy*
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Diabetes Mellitus, Type 2 / metabolism
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Diabetes Mellitus, Type 2 / pathology
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Diabetic Cardiomyopathies / chemically induced
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Diabetic Cardiomyopathies / prevention & control*
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Diet, High-Fat / adverse effects
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Dose-Response Relationship, Drug
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Glycation End Products, Advanced / antagonists & inhibitors
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Glycation End Products, Advanced / blood
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Heart Rate / drug effects
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Heart Ventricles / drug effects
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Heart Ventricles / metabolism
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Heart Ventricles / pathology
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Hypoglycemic Agents / administration & dosage
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Hypoglycemic Agents / adverse effects
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Hypoglycemic Agents / therapeutic use*
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Insulin Resistance
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Isoproterenol / poisoning
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Male
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Myocardial Infarction / chemically induced
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Myocardial Infarction / complications
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Myocardial Infarction / prevention & control*
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Organ Size / drug effects
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Overweight / complications
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Overweight / etiology
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Overweight / prevention & control
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Pioglitazone
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Random Allocation
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Rats, Wistar
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Receptor for Advanced Glycation End Products / antagonists & inhibitors
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Receptor for Advanced Glycation End Products / metabolism
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Thiazolidinediones / administration & dosage
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Thiazolidinediones / adverse effects
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Thiazolidinediones / therapeutic use*
Substances
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Adrenergic beta-Agonists
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Cardiotonic Agents
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Glycation End Products, Advanced
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Hypoglycemic Agents
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Receptor for Advanced Glycation End Products
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Thiazolidinediones
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Isoproterenol
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Pioglitazone