Effects of the New Aldose Reductase Inhibitor Benzofuroxane Derivative BF-5m on High Glucose Induced Prolongation of Cardiac QT Interval and Increase of Coronary Perfusion Pressure

• Published in: Journal of diabetes research Vol. 2016; no. 2016; pp. 1 - 8
• Main Authors: D'Amico, Michele, Rossi, Francesco, La Motta, Concettina, Sartini, S., Di Carluccio, N., Trotta, M. C., Maisto, R., Ferraro, B., Di Filippo, Clara, Ferraraccio, Franca
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 01-01-2016; Hindawi Limited
• Subjects: Aldehyde Reductase - antagonists & inhibitors; Aldehyde Reductase - metabolism; Animals; Antibodies; Benzofurans - pharmacology; Blood Pressure - drug effects; Cardiotoxicity; Cardiovascular disease; Coronary Circulation - drug effects; Coronary vessels; Diabetes; Diabetic Cardiomyopathies - enzymology; Diabetic Cardiomyopathies - physiopathology; Diabetic Cardiomyopathies - prevention & control; Electrodes; Enzyme Inhibitors - pharmacology; Forkhead Transcription Factors - metabolism; Gene expression; Glucose; Glucose - toxicity; Heart; Heart - drug effects; Heart - physiopathology; Heart Rate - drug effects; Histone Deacetylase Inhibitors - pharmacology; Hyperglycemia; Isolated Heart Preparation; Laboratory animals; Male; Metabolism; Myocardium - enzymology; Nerve Tissue Proteins - metabolism; Oxidative stress; Rats, Sprague-Dawley; Sinuses; Sirtuin 1 - antagonists & inhibitors; Sirtuin 1 - metabolism; Superoxide Dismutase - metabolism; United Kingdom > UK; United States > US; California
• ISSN: 2314-6745; 2314-6753
• DOI: 10.1155/2016/5281267

This study investigated the effects of the new aldose reductase inhibitor benzofuroxane derivative 5(6)-(benzo[d]thiazol-2-ylmethoxy)benzofuroxane (BF-5m) on the prolongation of cardiac QT interval and increase of coronary perfusion pressure (CPP) in isolated, high glucose (33.3 mM D-glucose) perfused rat hearts. BF-5m was dissolved in the Krebs solution at a final concentration of 0.01 μM, 0.05 μM, and 0.1 μM. 33.3 mM D-glucose caused a prolongation of the QT interval and increase of CPP up to values of 190 ± 12 ms and 110 ± 8 mmHg with respect to the values of hearts perfused with standard Krebs solution (11.1 mM D-glucose). The QT prolongation was reduced by 10%, 32%, and 41%, respectively, for the concentration of BF-5m 0.01 μM, 0.05 μM, and 0.1 μM. Similarly, the CPP was reduced by 20% for BF-5m 0.05 μM and by 32% for BF-5m 0.1 μM. BF-5m also increased the expression levels of sirtuin 1, MnSOD, eNOS, and FOXO-1, into the heart. The beneficial actions of BF-5m were partly abolished by the pretreatment of the rats with the inhibitor of the sirtuin 1 activity EX527 (10 mg/kg/day/7 days i.p.) prior to perfusion of the hearts with high glucose + BF-5m (0.1 μM). Therefore, BF-5m supplies cardioprotection from the high glucose induced QT prolongation and increase of CPP.