Effect of Combination Therapy of Alpha-Lipoic Acid, Ramipril, and Gliclazide in a Rat Model of Diabetic Cardiomyopathy Wonje, Quinsker Lariba

Abstract

Background Diabetic cardiomyopathy (DCM) is a prominent long-term diabetes mellitus complication, responsible for more than 20% of diabetic patient’s yearly death rate globally. Even though numerous anti-diabetic medications have improved the glycemic condition of diabetic individuals, the incidence of DCM remains high. In this research, the cardiac effects of anti diabetic medicine supplementation with alpha-lipoic acid (ALA) are examined in experimental DCM. Methods Following a 12-hour fast, a total of 44 male Sprague Dawley male rats were put into two groups: healthy control and diabetic groups, and glucose levels in blood were measured. The diabetic group was given an intraperitoneal (i.p) injection of nicotinamide and streptozotocin to induce type 2 diabetes mellitus (T2DM). The diabetic rats were given either ALA (60 mg/kg; ramipril (10 mg/kg;), gliclazide (15 mg/kg;) or all three drugs for 42 days after which they were euthanized, and samples collected for biochemical, histological and molecular analyses. Results T2DM induction caused pancreatic damage, high blood glucose, weight reduction, and DCM development, marked by cardiac fibrosis, vacuolation, degeneration as well as high plasma and cardiac levels of markers cardiac injury. Compared with diabetic control group, treatment with all three drugs protected the structure of pancreatic islets, preserved normoglycemia and body weight, and prevented DCM comparable with healthy controls (p > 0.05). In addition, combined treatment significantly reduced plasma interleukin-1, interleukin-6, and tumor necrotic factor-alpha, and improved antioxidant and lipid profile (p < 0.001). Finally, treatment with all three drugs markedly downregulated TGF-β1 and its effector proteins in the heart tissue (p <0.001). Conclusion The combined treatment provided protection against DCM via several pathways including inhibition of fibrotic pathway involving TGF-1/Smad signaling. This observation is applicable to clinical situations and could provide supplementary information on DCM pharmacological treatment in T2DM patients.