Abstract 13376: Oral Treatment With a Zinc Complex of Acetylsalicylic Acid Prevents Diabetic Cardiomyopathy in a Rat Model of Type 2 Diabetes

Abstract

Introduction: Type 2 diabetic patients are at an increased risk of cardiomyopathy and heart failure is a major cause of death amongst these patients. Growing evidence indicates that proinflammatory cytokines can cause sustained development of insulin resistance and anti-inflammatory medications may reverse this process. Hypothesis: We investigated the effects of an oral administration of zinc and acetylsalicylic acid in the form of bis(aspirinato)zinc(II) complex Zn(ASA)2 on different aspects of cardiac damage in the Zucker diabetic rat (ZDF), an experimental model of type 2 diabetic cardiomyopathy. Methods: The nondiabetic control and the diabetic ZDF rats were pretreated orally with vehicle or Zn(ASA)2 for 24 days. At the age of 30-32 weeks, both the electrical activity and the left ventricular (LV) structural/functional parameters were assessed via electrocardiogram and pressure volume (PV) conductance catheter system. Results: The Zn(ASA)2 treatment significantly decreased the blood glucose concentration (39.6±3.1 vs 50.4±2.6 mM), normalized the impaired LV contractility index (Emax 3.7±0.4 vs 1.9±0.6 mmHg/μl), the passive LV stiffness (end diastolic PV relationship: 0.064±0.008 vs 0.084±0.014 mmHg/μl), and the diastolic dysfunction (LV end diastolic pressure: 6.5±0.6 vs 7.9±0.7 mmHg). Furthermore, the ECG revealed a restoration of the prolonged corrected QT intervals (63±3 vs 83±4 ms, p<0.05) by Zn(ASA)2. A histological examination revealed an increase in the cardiomyocytes transverse cross section area in diabetic rats compared to the controls, which was significantly decreased after Zn(ASA)2. Furthermore, a significant increase in fibrotic formation was observed in the diabetic rats compared to controls, and Zn(ASA)2 administration showed similar collagen content in the ZDF+Zn(ASA)2 rats and in the nondiabetics. A significant increase in the density of TUNEL positive cell nuclei in the diabetic hearts, indicating DNA fragmentation, was significantly decreased by Zn(ASA)2. Additionally, in the diabetic heart, Zn(ASA)2 significantly decreased nitrotyrosine formation. Conclusions: The oral administration of Zn(ASA)2 may have therapeutic potential with the aim of preventing cardiac complications in type 2 diabetic patients.