Vitamin D reduces deposition of advanced glycation end-products in the aortic wall and systemic oxidative stress in diabetic rats

Abstract

AimsVitamin D may have an important role in reducing the risk of cardiovascular disease. Advanced glycation end-products (AGEs) such as Nε-(carboxymethyl)lysine (CML), have been implicated in diabetic vascular complications via oxidative stress-mediated pathways. We investigated the potential protective effect of vitamin D on CML accumulation in the diabetic aortic wall. To test the effects of vitamin D on systemic oxidative stress we also assessed liver oxidative stress index (OSI) and serum total antioxidant capacity (TAC). MethodsMale Wistar rats were assigned to three groups: control, untreated diabetes, and diabetes+cholecalciferol. Diabetes was induced by streptozotocin, followed by oral administration of cholecalciferol (500IU/kg) for 10 weeks in the treatment group. Aortic CML accumulation was determined by ELISA and immunohistochemical assays. OSI was assessed by measuring TAC and the level of total peroxides in the liver and serum using colorimetric assays. ResultsUntreated diabetes was associated with significantly elevated CML levels in the aortic wall (19.5±3.3 vs 10.2±4.7ng/mL), increased liver OSI (6.8±1.9 vs 3.1±0.7), and reduced serum TAC (0.4±0.1 vs 0.8±0.3mmol Trolox/L), in comparison with the control group. Cholecalciferol significantly blocked the accumulation of CML in the aortic wall (10.4±8.4 vs 19.5±3.3ng/mL), decreased liver OSI (4.2±1.4 vs 6.8±1.9), and improved serum TAC (1.0±0.2 vs 0.4±0.1mmol Trolox/L), compared with the untreated diabetic group. ConclusionsStreptozotocin-diabetes resulted in increased deposition of AGEs and increased oxidative stress in the serum and liver. Vitamin D supplementation may provide significant protection against oxidative stress-mediated vascular complications in diabetes.