Antioxidant and vascular effects of gliclazide in type 2 diabetic rats fed high...

• Author(s): Sena, C. M. ; Louro, T. ; Matafome, P. ; Nunes, E. ; Monteiro, P. ; Seiça, R.
• Date: 2009
• Persistent ID: http://hdl.handle.net/10316/12542
• Origin: Estudo Geral - Universidade de Coimbra
• Subject(s): Endothelium; Nitric Oxide; Diabetes mellitus; Gliclazide; Oxidative stress
• Document Type: Article
• Language: English

Description

Diabetes mellitus is characterized by oxidative stress, which in turn determines endothelial dysfunction. Gliclazide is a sulphonylurea antidiabetic drug with antioxidant effects due to its azabicyclo-octyl ring. It has been reported to potentially protect the vasculature through improvements in plasma lipid levels and platelet function. We hypothesized that gliclazide has a beneficial effect on endothelial function in Goto-Kakizaki rats (GK), an animal model of type 2 diabetes fed an atherogenic diet for 4 months. We evaluated the influence of gliclazide on both metabolic and oxidative status and NO-mediated vasodilation. GKAD rats showed increased oxidative stress and impaired endothelium-dependent vasodilation. GKAD rats treated with gliclazide showed increased sensitivity to NO-mediated vasodilation, a significant decrease in fasting glycemia and insulinemia, and a significant decrease in systemic oxidative stress. In conclusion, our results suggest that gliclazide treatment improves NO-mediated vasodilation in diabetic GK rats with dyslipidemia probably due to its antioxidant effects, although we cannot rule out substantial benefits due to a reduction in fasting blood glucose. The availability of a compound that simultaneously decreases hyperglycemia, hyperinsulinemia, and inhibits oxidative stress is a promising therapeutic candidate for the prevention of vascular complications of diabetes