title: 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.
abstract: 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.
authors.affiliation: Department of Experimental Medicine, Section of Pharmacology "L. Donatelli", Second University of Naples, 80138 Naples, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Di Filippo
authors.affiliation: Department of Experimental Medicine, Section of Pharmacology "L. Donatelli", Second University of Naples, 80138 Naples, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Ferraro
authors.affiliation: Department of Experimental Medicine, Section of Pharmacology "L. Donatelli", Second University of Naples, 80138 Naples, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Maisto
authors.affiliation: Department of Experimental Medicine, Section of Pharmacology "L. Donatelli", Second University of Naples, 80138 Naples, Italy.
authors.forename: M C
authors.initials: MC
authors.lastname: Trotta
authors.affiliation: Department of Experimental Medicine, Section of Pharmacology "L. Donatelli", Second University of Naples, 80138 Naples, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Di Carluccio
authors.affiliation: Department of Pharmacy, University of Pisa, 56126 Pisa, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Sartini
authors.affiliation: Department of Pharmacy, University of Pisa, 56126 Pisa, Italy.
authors.forename: C
authors.initials: C
authors.lastname: La Motta
authors.affiliation: Department of Clinical, Public and Preventive Medicine, Second University of Naples, 80138 Naples, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Ferraraccio
authors.affiliation: Department of Experimental Medicine, Section of Pharmacology "L. Donatelli", Second University of Naples, 80138 Naples, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Rossi
authors.affiliation: Department of Experimental Medicine, Section of Pharmacology "L. Donatelli", Second University of Naples, 80138 Naples, Italy.
authors.forename: M
authors.initials: M
authors.lastname: D'Amico
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D001572:Benzofurans / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D066126:Cardiotoxicity; D003326:Coronary Circulation / Q000187:drug effects*; D058065:Diabetic Cardiomyopathies / Q000201:enzymology / Q000503:physiopathology / Q000517:prevention & control*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005947:Glucose / Q000633:toxicity*; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D000067268:Isolated Heart Preparation; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D000071161:Forkhead Box Protein O1
chemical_list: D000449:Aldehyde Reductase; D001572:Benzofurans; D004791:Enzyme Inhibitors; D051858:Forkhead Transcription Factors; D005947:Glucose; D056572:Histone Deacetylase Inhibitors; D009419:Nerve Tissue Proteins; D056564:Sirtuin 1; D013482:Superoxide Dismutase; C000599765:5(6)-(benzo(d)thiazol-2- ylmethoxy)benzofuroxane; C074639:Foxo1 protein, rat; D000071161:Forkhead Box Protein O1; C488368:Sirt1 protein, rat
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