Abstract
BackgroundAzelnidipine (AZL), a long-acting dihydropyridine-based calcium antagonist, has been recently approved and used for treating ischemic heart disease and cardiac remodeling after myocardial infarction, however, its effect on hyperglycemia-induced cardiac damage has not been studied.MethodsThis study examined the effect of AZL on circulating markers of cardiac damage, altered lipid and cytokines profile and markers of oxidative stress including homocysteine in diabetic rats.ResultsSTZ induced diabetes caused a significant increase in blood glucose levels. It also resulted in an increase in the levels of homocysteine and cardiac damage markers, like Troponin-1, CK-MB, CK-NAC, uric acid, LDH and alkaline phosphatase. Moreover, there was an increase in the levels of proinflammatory cytokines like TNF-α, IFN-γ, and TGF-β and decrease in the levels of IL-4 and IL-10. Additionally, there was increase in the levels of cholesterol, triglycerides, LDL, VLDL and a decrease in HDL in these animals. There was an altered antioxidant enzyme profile which resulted in a notable increase in the levels of oxidative stress markers like lipid peroxides, nitric oxide and carbonylated proteins. Compared with the untreated diabetic rats, AZL treatment significantly reduced the levels of troponin-1 (P < 0.05), CK-MB (P < 0.05), CK-NAC (P < 0.05), uric acid (P < 0.05), LDH (P < 0.05) and alkaline phosphatase (P < 0.05). It also reduced the levels of the TNF-α (P < 0.05), IFN-γ (P < 0.05), and TGF-β (P < 0.05) and increased the levels of IL-4 (P < 0.05). A significant decrease in the serum cholesterol (P < 0.05), triglycerides (P < 0.05), LDL (P < 0.05), VLDL (P < 0.05) and a significant rise in levels of HDL (P < 0.05) was also observed. Treatment with AZL corrected the distorted antioxidant enzyme profile resulting in a significant decrease in the levels of lipid peroxides, nitric oxide and carbonylated proteins.ConclusionOur results indicate that AZL treatment can reduce the risk of hyperglycemia induced metabolic disorders and its role can be further extended to explore its therapeutic potential in diabetic patients with cardiac complications.
Highlights
Azelnidipine (AZL), a long-acting dihydropyridine-based calcium antagonist, has been recently approved and used for treating ischemic heart disease and cardiac remodeling after myocardial infarction, its effect on hyperglycemia-induced cardiac damage has not been studied
Our results indicate that AZL treatment can reduce the risk of hyperglycemia induced metabolic disorders and its role can be further extended to explore its therapeutic potential in diabetic patients with cardiac complications
AZL treatment resulted in a significant decrease in the left ventricular mass (LVM)/BW ratio indicating that AZL treatment prevents left ventricular hypertrophy
Summary
Azelnidipine (AZL), a long-acting dihydropyridine-based calcium antagonist, has been recently approved and used for treating ischemic heart disease and cardiac remodeling after myocardial infarction, its effect on hyperglycemia-induced cardiac damage has not been studied. The diabetic heart is characterized by diminished glucose utilization and increased fatty acid oxidation resulting in lipid accumulation in the myocardium [11,12]. This myocardial lipotoxicity results in alterations in the inflammatory cytokines levels and evokes a cascade of disparaging changes that leads to cardiac damage. The proinflammatory and profibrotic cytokine, TGF-b contributes to the in vivo cardiac electrical remodeling by decreasing cardiac muscle L-type calcium current and charge movement [19,20] These cytokine-induced cascades of events mechanistically contribute to cardiomyocyte apoptosis possibly due to disturbance of calcium homeostasis via redox regulatory mechanisms leading to extensive myocyte cell death
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