Resveratrol shows vasoprotective effect reducing oxidative stress without affecting metabolic disturbances in insulin-dependent diabetes of rabbits.
OBJECTIVE
Resveratrol has been shown to have vasoprotective effects by upregulating oxidative defense mechanisms in a variety of pathophysiological conditions. However, the effect of resveratrol on diabetic oxidative stress and vascular and metabolic abnormalities is not completely understood. Therefore, this study was designed to evaluate whether long-term resveratrol supplementation has a protective effect on vascular function and integrity in association with metabolic parameters and oxidative stress in insulin-dependent diabetes.


METHODS
Diabetes was induced in rabbits with alloxan and maintained for 8 weeks. We used a resveratrol dose of 5 mg/L (10 weeks, starting 14 days before alloxan injection) and 50 mg/L (8 or 10 weeks, starting concomitantly or 14 days before alloxan injection) in the drinking water of rabbits.


RESULTS
Relaxation to acetylcholine was impaired (control 75.6 ± 3.59%, versus diabetic 42.23 ± 2.53%) and contractions to phenylephrine increased (control 136.89 ± 2.27%, versus diabetic 159.37 ± 6.27%) in aortas from diabetic animals. These changes were associated with increased basal or NAD(P)H-induced superoxide production, as well as lipid peroxide and superoxide dismutase (SOD) levels in the aortic samples. The maximal relaxation to acetylcholine improved by 75.74 ± 9.04% in diabetic rabbits treated with resveratrol. The increased contractions to phenylephrine were not restored to control values after resveratrol treatments, but sensitivity to the contractions tended to decrease. Resveratrol increased nitrite/nitrate levels and suppressed basal or NAD(P)H-induced superoxide production and lipid peroxide levels in the aortas. Importantly, resveratrol increased serum insulin levels without affecting blood glucose and the lipid profile in diabetic rabbits. Using electron microscopic examinations, resveratrol was found to markedly protect the endothelial integrity from diabetes.


CONCLUSIONS
Overall, there was no noticeable difference between resveratrol treatment groups on the recovery from diabetes. Our results indicate that resveratrol alleviates type 1 diabetes-induced vasculopathy by decreasing vascular oxidative stress and thereby increasing the bioavailability of nitric oxide without changing metabolic abnormalities.
Akar
Fatma
F
Department of Pharmacology, Faculty of Pharmacy, Gazi University, Etiler, Ankara, Turkey. fakar@gazi.edu.tr
Pektas
M Bilgehan
MB
Tufan
Can
C
Soylemez
Selen
S
Sepici
Aylin
A
Ulus
A Tulga
AT
Gokalp
Burcu
B
Ozturk
Kamile
K
Surucu
H Selcuk
HS
D000109:Acetylcholine / Q000097:blood / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002374:Catalase / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000378:metabolism; D004967:Estrogens / Q000097:blood; D007328:Insulin / Q000097:blood; D008054:Lipid Peroxides / Q000032:analysis / Q000502:physiology; D008055:Lipids / Q000097:blood / Q000502:physiology; D008297:Male; D009249:NADP / Q000378:metabolism; D009569:Nitric Oxide / Q000032:analysis / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D011817:Rabbits; D000077185:Resveratrol; D013267:Stilbenes / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D013482:Superoxide Dismutase / Q000378:metabolism; D013739:Testosterone / Q000097:blood; D013997:Time Factors; D014652:Vascular Diseases / Q000188:drug therapy* / Q000517:prevention & control
D000975:Antioxidants; D001786:Blood Glucose; D004967:Estrogens; D007328:Insulin; D008054:Lipid Peroxides; D008055:Lipids; D013267:Stilbenes; D009569:Nitric Oxide; D013739:Testosterone; D009249:NADP; D002374:Catalase; D052250:Nitric Oxide Synthase Type III; D013482:Superoxide Dismutase; D000109:Acetylcholine; D000077185:Resveratrol