Dietary Blueberries Attenuate Atherosclerosis in Apolipoprotein E-Deficient Mice by Upregulating Antioxidant Enzyme Expression

Abstract

Protective effects of blueberries (BB) against atherosclerosis and potential underlying mechanisms in reducing oxidative stress were examined in apoE-deficient (apoE(-/-)) mice. ApoE(-/-) mice were fed an AIN-93G diet (CD) or CD formulated to contain 1% freeze-dried whole BB for 20 wk. The mean lesion area for apoE(-/-) mice fed BB was reduced by 39% (P < 0.001) in the aorta sinus and 58% (P < 0.001) in the descending aorta compared with CD-fed mice. These atheroprotective effects were independent of the serum lipid profile or total antioxidant capacity (as measured by oxygen radical absorbance capacity). The concentration of a biomarker of lipid peroxidation, F(2)-isoprostane, was lower in liver of BB-fed mice (P < 0.05). Genes analyzed by RT-PCR array showed that 4 major antioxidant enzymes in aorta [superoxide dismutase (SOD) 1, SOD2, glutathione reductase (GSR), and thioredoxin reductase 1] were upregulated in BB-fed mice. Enzyme activities of SOD and GSR were greater (P < 0.05) in liver and/or serum of BB-fed mice than those of CD-fed mice. In addition, serum paraoxonase 1 activity in serum of BB-fed mice was also greater than that of CD-fed mice (P < 0.05) at the end of the study. These results suggest a protective effectiveness of BB against atherosclerosis in this apoE(-/-) mouse model. The potential mechanisms may involve reduction in oxidative stress by both inhibition of lipid peroxidation and enhancement of antioxidant defense.

Nutrient Analysis Critical Control Point (NACCP): Hazelnut as a Prototype of Nutrigenomic Study

“…In our work the transcription levels of GSR were increased after hazelnut consumption (p ≤ 0.05), suggesting a protective role against oxidative stress and atherogenic process. Our results could be in part supported by the recent work of Wu X. et al [34,35] in which they found that an up-regulation of GSR gene in mice with diet enriched of blueberry indicated a protective role of these fruits against oxidative stress. This result could be easily compared with our result in which we found an up-regulation of GSR in subjects with a diet enriched of hazelnuts.…”

Effect of dietary blueberry (Vaccinium ashei Reade) leaves on serum and hepatic lipid levels in rats

“…Kalt et al also showed that pigs fed diets supplemented with 1 , 2 , and 4 freeze-dried blueberry leaf powder showed a decrease in total, LDL-, and HDLcholesterol levels, although no dose response was evident 24 . The antiatherosclerotic effect of dietary freezedried blueberry leaf powder has been shown at the 1 dietary level in apolipoprotein E-deficient mice, although this effect was independent of an altered serum lipid profile or total antioxidant capacity 25 . Taken together, the observations made in this study and the observation regarding a potent antihypertensive effect of BL reported by Sakaida et al 13 indicate that BL is a promising candidate for a functional human food.…”

Hawthorn Fruit Attenuates Atherosclerosis by Improving the Hypolipidemic and Antioxidant Activities in Apolipoprotein E-Deficient Mice

“…Decreasing the production of ox-LDL by inhibiting LDL oxidation and taking measures to antagonize ox-LDL may be means of preventing and controlling atherosclerosis. Research has demonstrated the protective effects of blueberries against atherosclerosis in apolipoprotein E-deficient (apoE −/− ) mice; the potential mechanisms may involve a reduction in oxidative stress due to both inhibition of lipid peroxidation and the enhancement of antioxidant defense 18) . In recent studies, extracts of hawthorn fruit have been shown to inhibit LDL and liposome oxidation in cell cultures and significantly reduce the levels of lipid hydroperoxides in humans 19,20) .…”