Naringin ameliorates endothelial dysfunction in fructose-fed rats

Abstract

High fructose consumption is associated with metabolic disorders including hyperglycemia and dyslipidemia, in addition to endothelial dysfunction. Naringin, a flavonoid present in citrus fruit, has been reported to exhibit lipid lowering, antioxidant, and cardiovascular protective properties. Therefore, the present study investigated the effect of naringin on fructose-induced endothelial dysfunction in rats and its underlying mechanisms. Male Sprague-Dawley rats were given 10% fructose in drinking water for 12 weeks, whereas control rats were fed drinking water alone. Naringin (100 mg/kg) was orally administered to fructose fed rats during the last 4 weeks of the study. Following 12 weeks, blood samples were collected for measurement of blood glucose, serum lipid profile and total nitrate/nitrite (NOx). Vascular function was assessed by isometric tension recording. Aortic expression of endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (p-eNOS), and nitrotyrosine were evaluated by western blot analysis. Fructose feeding induced increased levels of blood glucose, total cholesterol, triglyceride, and low density lipoprotein. In rat aortae, fructose reduced acethycholine-induced vasorelaxation, without affecting sodium nitroprusside-induced vasorelaxation. Treatment of fructose-fed rats with naringin restored fructose-induced metabolic alterations and endothelial dysfunction. Fructose-fed rats also exhibited decreased serum NOx level, reduced eNOS and p-eNOS protein expression, and enhanced nitrotyrosine expression in aortae. These alterations were improved by naringin treatment. The results of the present study suggested that naringin treatment preserves endothelium-dependent relaxation in aortae from fructose fed rats. This effect is primarily mediated through an enhanced NO bioavailability via increased eNOS activity and decreased NO inactivated to peroxynitrite in aortae.

Keywords: endothelial dysfunction; fructose-fed rats; naringin; nitric oxide; nitrotyrosine.

Figure 1.

Effect of naringin treatment on concentration response curves to the (A) endothelium-dependent dilator ACh and the (B) endothelium-independent dilator SNP in aortic rings from fructose fed rats. In each group of experiments the aortic rings were precontracted to a similar level using PE (50±2% of KPSS). ACh, acetylcholine; SNP, sodium nitroprusside; C, control rats; F, fructose-fed rats; FN, fructose fed rats treated naringin; PE, phenylephrine.

Figure 2.

Concentration-response curves for acetylcholine in phenylephrine-contracted aortic rings, alone (▪) or in the presence of indomethacin (∆) or NG-nitro-l-arginine (l-NNA; ○) in (A) C group, (B) F group and (C) FN group. All data are shown as the mean ± SEM. ACh, acetylcholine; C, control rats; F, fructose-fed rats; FN, fructose fed rats treated naringin; PE, phenylephrine.

Figure 3.

Protein expression of (B) eNOS, (C) phosphorylated eNOS at Ser1177 residue, and (D) nitrotyrosine in aortic tissues from control (C), fructose (F), and fructose plus naringin (FN) groups. (A) Representative western blottings. Results are expressed as mean ± SEM (n=6 per group) and presented as percentage of control value. *P<0.05 compared with control group, ^#P<0.05 compared with F group. eNOS, endothelial nitric oxide synthase.