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    Effect of vitamin E and C supplementation combined with oral antidiabetic therapy on the endothelial dysfunction in the neonatally streptozotocin injected diabetic rat
    (Wiley, 2006) Alper, Gulinnaz; Olukman, Murat; İrer, Seda; Çağlayan, Osman; Duman, Erdal; Yılmaz, Candeğer; Ülker, Sibel
    Background This study investigates the contribution of vitamin supplementation to the efficacy of oral antidiabetic therapy on the reversal of endothelial dysfunction in a model of type-2 diabetes in rat. Methods Diabetes was induced by streptozotocin injection to neonatal rats which were breastfed for 4 weeks, then fed 6 weeks with normal food or food supplemented with 2% vitamin E and 4% vitamin C. Some diabetic rats were treated with gliclazide for 6 weeks. Endothelium-dependent and -independent relaxations to acetylcholine and sodium nitroprusside (SNP) were recorded in thoracic aortic rings. Plasma insulin, HbA(1c) and antioxidant vitamins (A, C and E); plasma and aortic malondialdehyde (NIDA) levels were determined. Results Induction of diabetes resulted in decreased body weight and increased blood glucose, plasma insulin and HbA(1c) levels compared to controls. Acetylcholine relaxation was impaired in diabetic aorta, while SNP relaxation remained unchanged. Aortic MDA level was significantly higher, while plasma vitamin levels were lower in diabetic rats. Diminished acetylcholine response, enhanced aortic MDA level and decreased plasma vitamin levels were all restored after gliclazide and/or vitamin therapy. However, vitamin supplementation in control rats significantly impaired acetylcholine relaxations and increased aortic MDA levels. Conclusions Apparently, a selective endothelial dysfunction accompanies the imbalance in oxidant/antioxidant status in the type-2 diabetes model of rat and gliclazide and/or vitamin supplementation improves the impairment in diabetic vasculature. However, vitamin supplementation triggers oxidative stress in normal aortic tissue, thereby, leads to endothelial dysfunction; indicating that nutritional extra-supplementation of antioxidant vitamins isn't advisable for normal subjects, although it's beneficial in disease status. Copyright (c) 2005 John Wiley & Sons, Ltd.