title: Vitamin D reduces deposition of advanced glycation end-products in the aortic wall and systemic oxidative stress in diabetic rats.
abstract: OBJECTIVE
  Vitamin 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).
  
  
  METHODS
  Male Wistar rats were assigned to three groups: control, untreated diabetes, and diabetes+cholecalciferol. Diabetes was induced by streptozotocin, followed by oral administration of cholecalciferol (500 IU/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.
  
  
  RESULTS
  Untreated diabetes was associated with significantly elevated CML levels in the aortic wall (19.5 ± 3.3 vs 10.2 ± 4.7 ng/mL), increased liver OSI (6.8 ± 1.9 vs 3.1 ± 0.7), and reduced serum TAC (0.4 ± 0.1 vs 0.8 ± 0.3 mmol 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 ± 3.3 ng/mL), decreased liver OSI (4.2 ± 1.4 vs 6.8 ± 1.9), and improved serum TAC (1.0 ± 0.2 vs 0.4 ± 0.1 mmol Trolox/L), compared with the untreated diabetic group.
  
  
  CONCLUSIONS
  Streptozotocin-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.
authors.affiliation: Department of Cardiology, University of Tartu, 8 Puusepa Street, Tartu 51014, Estonia. erik.salum@gmail.com
authors.forename: Erik
authors.initials: E
authors.lastname: Salum
authors.forename: Jaak
authors.initials: J
authors.lastname: Kals
authors.forename: Priit
authors.initials: P
authors.lastname: Kampus
authors.forename: Tiit
authors.initials: T
authors.lastname: Salum
authors.forename: Kersti
authors.initials: K
authors.lastname: Zilmer
authors.forename: Marina
authors.initials: M
authors.lastname: Aunapuu
authors.forename: Andres
authors.initials: A
authors.lastname: Arend
authors.forename: Jaan
authors.initials: J
authors.lastname: Eha
authors.forename: Mihkel
authors.initials: M
authors.lastname: Zilmer
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D014807:Vitamin D / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D017127:Glycation End Products, Advanced; D014807:Vitamin D