Effect of vitamin E and C supplementation combined with oral antidiabetic therapy on the endothelial dysfunction in the neonatally streptozotocin injected diabetic rat.
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 (MDA) 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.
Alper
Gülinnaz
G
Department of Biochemistry, Faculty of Medicine, Ege University, Izmir, Turkey. gulinnaz.alper@ege.edu.tr
Olukman
Murat
M
Irer
Seda
S
Cağlayan
Osman
O
Duman
Erdal
E
Yilmaz
Candeğer
C
Ulker
Sibel
S
D000109:Acetylcholine / Q000494:pharmacology; D000284:Administration, Oral; D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000378:metabolism; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D019587:Dietary Supplements; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D006442:Glycated Hemoglobin / Q000032:analysis; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D008315:Malondialdehyde / Q000097:blood; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D013311:Streptozocin / Q000008:administration & dosage; D014664:Vasodilation / Q000187:drug effects; D014810:Vitamin E / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*
D000109:Acetylcholine; D000975:Antioxidants; D001205:Ascorbic Acid; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008315:Malondialdehyde; D009599:Nitroprusside; D013311:Streptozocin; D014810:Vitamin E