Abstract
Pharmacological Modulation of Long Cardiac QT Interval in Ex Vivo and in Vitro Experimental Models
Highlights
About the 90% of Long QT Syndrome (LQTS) cases are related to alterations of the 3 main genes codifying cardiac sodium and potassium channels: KCNQ1, KCNH2 and SCN5A genes [4,5]
One of the most important risk factor influencing Long QT prolongation is hyperglycemia: high glucose levels leads to ventricular instability both in healthy and non diabetic patients and to significant haemodynamic and electric perturbations in streptozotocin-diabetic rats, interestingly reversed by the freeradicals scavenger glutathione [11,12,13,14]
While under normoglycemic conditions (3.8-6.1 mmol/L) only about 3% of cellular glucose is converted to s orbital by aldose reductase 2 (ALR2), when hyperglycemic conditions occur (>7 mmol/L) more than 30% of glucose is shunted to the polyol pathway
Summary
Maria Consiglia Trotta*, Rosa Maisto, Nicola Perrotta, Michele D’Amico and Clara Di Filippo. Previous studies showed that the selective inhibition of the endogenous aldose reductase 2 (ALR2) activities, responsible of the oxidative heart damage following diabetes, could be a therapeutic treatment for the high glucose-related cardiac alterations. The newly synthetized ALR2 inhibitor, the benzofuroxane derivative 5(6)-(benzo[d]thiazol-2-ylmethoxy)benzofuroxane (BF-5m), dose-dependently reduced the long cardiac QT interval in isolated rat hearts perfused with high glucose, by increasing in parallel the expression and activity of endogenous antioxidant pathways and free radical scavengers such as SIRT1 and its targets MnSOD and FOXO-1.
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