Addition of the Aldose Reductase Inhibitor Benzofuroxane Derivative BF-5m to Prolonged and Moderate Exercise Training Enhanced Protection of the Rat Heart From Type-1 Diabetes

In this study, treatment of diabetic rats with ALR2 inhibitor BF-5m combined with prolonged exercise provided superior cardioprotection, as evidenced by prevention of onset and progression of cardiovascular dysfunction induced by hyperglycaemia. Co-treatment with BF-5m and exercise was more effective than either treatment alone. An explanation of this phenomenon may reside in a synergic action of BF-5m with the physical exercise against the oxidative stress and ROS overproduction induced by diabetes. Functional to this point it is well known beneficial effect of moderate exercise training on the increased formation of advanced glycation end-products (AGEs) and on the activation of protein kinase C (PKC) (Korzick et al., 2004; Gu et al., 2014), other two important pathways involved in diabetic ROS overproduction. BF-5m combined with the moderate exercise training may overwhelm the oxidative imbalance in diabetic rats if compared to the inhibition of the aldose reductase 2 alone. The advantages of the combined therapies were as follow: cardiac QT was normalized to a greater extent in response to co-treatment; cardiac ejection fraction was increased by 33% in response to co-treatment compared to sedentary vehicle-treated rats, with a good recovery of systolic function; levels of SERCA2 and MnSOD were significantly increased in response to co-treatment with BF-5m and exercise; and insulin release was increased in the co-treatment group. Furthermore, immunohistochemical analysis ...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research