Antioxidant and vascular effects of gliclazide in type 2 diabetic rats fed high-fat diet.
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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Institute of Physiology, University of Coimbra, Coimbra, Portugal. csena@ci.uc.pt
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D000080242:8-Hydroxy-2'-Deoxyguanosine; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001835:Body Weight; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D003925:Diabetic Angiopathies / Q000378:metabolism / Q000517:prevention & control*; D004041:Dietary Fats / Q000494:pharmacology*; D004195:Disease Models, Animal; D050171:Dyslipidemias / Q000150:complications / Q000378:metabolism; D005907:Gliclazide / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D011922:Rats, Mutant Strains; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D000975:Antioxidants; D004041:Dietary Fats; D007004:Hypoglycemic Agents; D014665:Vasodilator Agents; D009569:Nitric Oxide; D000080242:8-Hydroxy-2'-Deoxyguanosine; D005907:Gliclazide; D003849:Deoxyguanosine; D000109:Acetylcholine