Abstract
Abstract Backgrounds: Ranolazine had two main functions: blocking cardiac late sodium channels and / or inhibition of 3- ketoacyl coenzyme A thiolase, an important enzyme in s-oxidation of fatty acids. Diabetic cardiomyopathy is a complication, defined as cardiac dysfunction without the involvement of epicardial vessels. In this study, the effect of ranolazine on fatty acid oxidation was investigated in diabetic rats induced by streptozotocin. Methods: After 8 weeks of diabetic induction, the effect of ranolazine on fatty acid oxidation rate was studied. Statistical data were analyzed using Mann-Whitney test. Results: The activity of s-oxidation enzymes were inhibited by ranolazine in the normal rat hearts significantly, while no significant inhibition was seen in diabetic ones. Conclusion: Our data suggest that the clinical efficacy of ranolazine in diabetic patients is associated with a mechanism other than inhibition of the s-oxidation pathway activity, although various hypotheses exist in the literature.
Highlights
The incidence of mortality from cardiovascular diseases is high in diabetic patients
Insulin deficiency makes major abnormalities in glucose and fatty acids metabolism in myocardial cells which activates the ß-oxidation of free fatty acids
Hyperglycemia induced cardiomyopathy and increased significantly heart to body weight ratio after two months of diabetes induction in experimental rats [11,12] as we shown in the present study
Summary
The incidence of mortality from cardiovascular diseases is high in diabetic patients. Metabolism of substrate shifts from glucose to the higher level of free fatty acids due to hyperlipidemia and insulin resistance. Diabetes is marked by decreases in the intensity of glucose transport, glucose oxidation and phosphorylation, plus decreases in ATP levels in cardiac myocytes [2]. Fatty acid oxidation produces 90% of ATP in diabetic hearts. As the rate of glycolysis decreases, production of lactate and H+ increases that leads to intracellular acidosis. Under this condition, reduced activity of Na+ / K+ATPase and Na+- Ca2+ exchanger result sodium and calcium overload and may enhance myocyte damage [4]. It is important to find some new treatments that partially inhibit extensive fatty acid ß-oxidation and promote glucose consumption in diabetic heart
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