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Antioxidant and vascular effects of gliclazide in type 2 diabetic rats fed high-at diet
C. M. Sena, T. Louro, P. Matafome, E. Nunes, P. Monteiro, R. Seiça
Jazyk angličtina Země Česko
Free Medical Journals od 1998
ProQuest Central od 2005-01-01
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- MeSH
- acetylcholin farmakologie MeSH
- antioxidancia farmakologie MeSH
- deoxyguanosin analogy a deriváty moč MeSH
- diabetes mellitus 2. typu farmakoterapie komplikace metabolismus MeSH
- diabetické angiopatie metabolismus prevence a kontrola MeSH
- dietní tuky farmakologie MeSH
- dyslipidemie komplikace metabolismus MeSH
- financování organizované MeSH
- gliklazid farmakologie MeSH
- hypoglykemika farmakologie MeSH
- krysa rodu rattus MeSH
- modely nemocí na zvířatech MeSH
- mutantní kmeny potkanů MeSH
- oxid dusnatý metabolismus MeSH
- oxidační stres účinky léků MeSH
- potkani Wistar MeSH
- tělesná hmotnost MeSH
- vazodilatace účinky léků MeSH
- vazodilatancia farmakologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
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.
Lit.: 27
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- $a Institute of Physiology, University of Coimbra, Coimbra
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- $a Lit.: 27
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- $a 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.
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