Resveratrol Shows Vasoprotective Effect Reducing Oxidative Stress Without Affecting Metabolic Disturbances in Insulin-dependent Diabetes of Rabbits
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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.
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.
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.
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.
Key wordsResveratrol Endothelial and vascular function Superoxide Nitric oxide Insulin Alloxan Diabetic rabbits
This study was supported by a grant from TUBITAK 2008, Project No: 105 S431.
Conflict of interest
The authors state no conflict of interest.
- 6.Coskun B, Soylemez S, Parlar AI, Ulus AT, Katircioglu SF, Akar F. Effect of resveratrol on nitrate tolerance in isolated human internal mammary artery. J Cardiovas Pharmacol. 2006;47:437–45.Google Scholar
- 30.Jager U, Nguyen-Doung H. Relaxant effect of trans-resveratrol on isolated porcine coronary arteries. Arzneim Forsch Drug Res. 1999;49:207–11.Google Scholar
- 32.Rush JWE, Quadrilatero J, Levy AS, Ford RJ. Chronic resveratrol enhances endothelium-dependent relaxation but does not alter eNOS levels in aorta of spontaneously hypertensive rats. Exp Biol Med. 2007;232:814–22.Google Scholar
- 34.Schiller NK, Timothy AM, Chen IL, et al. Endothelial cell regrowth and morphology after balloon catheter injury of alloxan-induced diabetic rabbits. Am J Physiol Heart Circ Physiol. 1999;277:H740–8.Google Scholar