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    Effect of I-deprenyl and gliclazide on oxidant stress/antioxidant status and DNA damage in a diabetic rat model
    (Taylor & Francis Inc, 2005) Alper, Gülinnaz; İrer, Seda; Duman, Erdal; Çağlayan, Osman; Yılmaz, Candeğer
    Background: This study investigates the possible effect of monoamine oxidase inhibitor ( MAOI), selegyline ( 1-deprenyl), in combination with oral antidiabetic-gliclazide ( OAD), in preventing oxidative stress in streptozotocin-induced diabetes model in male Swiss Albino rats by measuring oxidant stress/DNA damage and antioxidant levels. Methods: Diabetic rats were divided into four groups ( n = 10) as ( 1) diabetic untreated ( DM), ( 2) deprenyl treated ( DM + D), ( 3) gliclazide treated ( DM + O), and ( 4) gliclazide and deprenyl treated ( DM + O + D). Controls were divided into two groups ( n = 8) ( 1) untreated ( C), and ( 2) deprenyl treated ( C + D). Gliclazide 5 mg/kg and/or MAOI 0.25 mg/kg daily were given orally by gavage for 4 weeks. At the end of the 12th week, catalase and superoxide dismutase ( SOD) levels in erythrocyte lysates ( EL); total antioxidant status ( TAS), 8-hydroxy-deoxyguanosine ( 8-OHdG), malondialdehyde ( MDA), and vitamin A and E levels in plasma, MDA, and MAO in liver homogenates were determined. Results: Diabetic rats showed a decrease in EL-SOD, plasma TAS, and vitamin E, and an increase in plasma 8-OHdG, plasma, and liver MDA levels ( p < 0.05). Gliclazide and/or deprenyl decreased 8OHdG levels and increased antioxidant levels and survival when compared with untreated diabetic rats ( p < 0.05). The lowest 8-OHdG levels were determined in the DM + O + D group. Conclusions: The combined treatment of deprenyl and gliclazide may contribute to the control of the physiopathological mechanisms underlying both the process of aging and type 2 diabetes by reducing oxidant stress and DNA damage, improving antioxidant status, and increasing survival, and may have implications for further clinical studies.
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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.