Abstract
Moderate exercise training may not be sufficient to exert beneficial effects on the cardiovascular system because of the long-term multifactorial etiology of diabetic complications. The addition of a proper pharmacological tool to the physical exercise should improve the outcomes of the diabetic damage. Here it is shown that 8 weeks exercise training of type 1 diabetic Sprague-Dawley (SD) rats resulted in a significantly increased heart rate, a 14% increase in the left ventricular ejection fraction (LVEF) increased plasma insulin levels and a 13% decrease in plasma glucose with respect to sedentary animals. The training also resulted in a 22% reduction in cardiac QT interval from a diabetic sedentary value of 185 ± 19 ms. Treatment of trained rats with the new antioxidant and NO-releasing aldose reductase 2 inhibitor 5(6)-(benzo[d]thiazol-2-ylmethoxy) benzofuroxane BF-5m, 20 mg/kg/day, added a further and significant (P < 0.01 vs. sedentary) increase of the LVEF up to 38% at 8 week time point. The long QT interval recorded in trained rats was reduced to further 12% by addition to the training of pharmacological treatment with 20 mg/kg/day BF-5m. At this time, the association of the two treatments improved the expression into the cardiac tissue of sarcoplasmic reticulum Ca2+ ATPase 2 (SERCA2) and manganese superoxide dismutase (MnSOD), and reduced the fibrosis.
Highlights
Diabetes mellitus, a common disease in most developed countries, causes biochemical and pathological complications
The present study showed that the benzofuroxane derivative molecule BF-5m, combined with prolonged moderate physical exercise enhances heart protection from type-1 diabetes
Physical activity is an universally accepted treatment strategy that is often used in combination with pharmacological approaches, and as a monotherapy for treatment of metabolic disorders, and leads to reduction of oxidative stress, (Leal et al, 2018) which is a contributor to development, and subsequent complications of diabetes (Le Lay et al, 2014; Shaw et al, 2014)
Summary
A common disease in most developed countries, causes biochemical and pathological complications. Addition of a proper pharmacological agent to physical exercise should improve outcomes related to diabetic damage. In this context, it is investigated here the addition of the selective aldose reductase 2 inhibitor benzofuroxane derivative, BF-5m, (Sartini et al, 2012) to prolonged moderate exercise training. BF-5m effectively treats diabetic symptoms in vitro (Sartini et al, 2012) and in models of inflammation-based pathologies (Di Filippo et al, 2014), since aldose reductase 2 is the rate-limiting enzyme of the polyol
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