A blueberry-enriched diet attenuates nephropathy in a rat model of hypertension via reduction in oxidative stress

Abstract

Objective and background: To assess renoprotective effects of a blueberry-enriched diet in a rat model of hypertension. Oxidative stress (OS) appears to be involved in the development of hypertension and related renal injury. Pharmacological antioxidants can attenuate hypertension and hypertension-induced renal injury; however, attention has shifted recently to the therapeutic potential of natural products as antioxidants. Blueberries (BB) have among the highest antioxidant capacities of fruits and vegetables.

Methods and results: Male spontaneously hypertensive rats received a BB-enriched diet (2% w/w) or an isocaloric control diet for 6 or 12 weeks or 2 days. Compared to controls, rats fed BB-enriched diet for 6 or 12 weeks exhibited lower blood pressure, improved glomerular filtration rate, and decreased renovascular resistance. As measured by electron paramagnetic resonance spectroscopy, significant decreases in total reactive oxygen species (ROS), peroxynitrite, and superoxide production rates were observed in kidney tissues in rats on long-term dietary treatment, consistent with reduced pathology and improved function. Additionally, measures of antioxidant status improved; specifically, renal glutathione and catalase activities increased markedly. Contrasted to these observations indicating reduced OS in the BB group after long-term feeding, similar measurements made in rats fed the same diet for only 2 days yielded evidence of increased OS; specifically, significant increases in total ROS, peroxynitrite, and superoxide production rates in all tissues (kidney, brain, and liver) assayed in BB-fed rats. These results were evidence of "hormesis" during brief exposure, which dissipated with time as indicated by enhanced levels of catalase in heart and liver of BB group.

Conclusion: Long-term feeding of BB-enriched diet lowered blood pressure, preserved renal hemodynamics, and improved redox status in kidneys of hypertensive rats and concomitantly demonstrated the potential to delay or attenuate development of hypertension-induced renal injury, and these effects appear to be mediated by a short-term hormetic response.

Figure 1. Blueberry-enriched diet delays the progression of hypertension.

Mean arterial and systolic blood pressures were assessed in rats fed a control diet or a blueberry-enriched diet for 6 weeks (A) or 12 weeks (B). ^* p<0.05 vs. SC; ^† p<0.05 vs. SBB.

Figure 2. Blueberry-enriched diet improves glutathione activity in hypertensive rats.

Glutathione activities were assessed in renal cortical and medullary tissues of rats fed a control diet or a blueberry-enriched diet for 6 weeks (A) or 12 weeks (B). ^*p<0.05; ^** p<0.01; ^*** p<0.001.

Figure 3. Blueberry-enriched diet improves catalase activity in hypertensive rats.

Catalase activities were assessed in renal cortical and medullary tissues of rats fed a control diet or a blueberry-enriched diet for 6 weeks (A) or 12 weeks (B). ^*p<0.05; ^** p<0.01; ^*** p<0.001.

Figure 4. Blueberry-enriched diet improves renal pathology in hypertensive rats fed for 6 weeks.

Trichrome-stained kidney sections were evaluated by a veterinary pathologist who was blinded to experimental conditions. Kidneys from (A) WC and (B) WBB rats exhibited similar histological appearance, with mild pathologic changes. Kidneys from (C) SC rats exhibited greater incidence and severity of pathologic change, while kidneys from (D) SBB rats exhibited very little pathologic change. Scale bar  =  200 um. F  =  fibrosis, H  =  vascular smooth muscle hypertrophy, D  =  tubular degeneration and ectasia, and M  =  glomerular parietal metaplasia.

Figure 5. Blueberry-enriched diet improves renal pathology in hypertensive rats fed for 12 weeks.

Trichrome-stained kidney sections were evaluated by a veterinary pathologist who was blinded to experimental conditions. In all four 12-week groups, the amount of interstitial, periarterial, and periglomerular fibrosis was greater than at six weeks. The SC rat kidneys (C) had severe arterial changes, with evidence of hypoxia. Kidneys from the SC rats also had the most severe fibrosis, arterial myointimal hyperplasia, tubular degeneration and necrosis, and evidence of hemoglobin and proteinaceous casts. The SBB rat kidneys (D) did exhibit arterial myointimal hyperplasia, though it was much less severe. Kidneys of WC (A) and WBB (B) rats fed for 12 weeks exhibited much less severe changes, but showed the same trends. Scale bar  =  200 um. F  =  fibrosis, H  =  vascular smooth muscle hypertrophy, T  =  organizing thrombus, D  =  tubular degeneration and ectasia, and M  =  glomerular parietal metaplasia.