Azelnidipine protects myocardium in hyperglycemia-induced cardiac damage

Background: 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, however, its effect on hyperglycemia-induced cardiac damage has not been studied. Methods: This 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. Results: STZ 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-alpha, IFN-gamma, and TGF-beta 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-alpha (P < 0.05), IFN-gamma (P < 0.05), and TGF-beta (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. Conclusion: 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.