High amylose resistant starch diet ameliorates oxidative stress, inflammation, and progression of chronic kidney disease - PubMed (original) (raw)

High amylose resistant starch diet ameliorates oxidative stress, inflammation, and progression of chronic kidney disease

Nosratola D Vaziri et al. PLoS One. 2014.

Abstract

Inflammation is a major mediator of CKD progression and is partly driven by altered gut microbiome and intestinal barrier disruption, events which are caused by: urea influx in the intestine resulting in dominance of urease-possessing bacteria; disruption of epithelial barrier by urea-derived ammonia leading to endotoxemia and bacterial translocation; and restriction of potassium-rich fruits and vegetables which are common sources of fermentable fiber. Restriction of these foods leads to depletion of bacteria that convert indigestible carbohydrates to short chain fatty acids which are important nutrients for colonocytes and regulatory T lymphocytes. We hypothesized that a high resistant starch diet attenuates CKD progression. Male Sprague Dawley rats were fed a chow containing 0.7% adenine for 2 weeks to induce CKD. Rats were then fed diets supplemented with amylopectin (low-fiber control) or high fermentable fiber (amylose maize resistant starch, HAM-RS2) for 3 weeks. CKD rats consuming low fiber diet exhibited reduced creatinine clearance, interstitial fibrosis, inflammation, tubular damage, activation of NFkB, upregulation of pro-inflammatory, pro-oxidant, and pro-fibrotic molecules; impaired Nrf2 activity, down-regulation of antioxidant enzymes, and disruption of colonic epithelial tight junction. The high resistant starch diet significantly attenuated these abnormalities. Thus high resistant starch diet retards CKD progression and attenuates oxidative stress and inflammation in rats. Future studies are needed to explore the impact of HAM-RS2 in CKD patients.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1

Figure 1. Representative photomicrographs of the PAS & H&E stained kidney sections in a normal control rat, a CKD rat fed low fiber, and a CKD rat fed high resistant starch diet [Magnification x10].

The kidney tissue in the CKD animals exhibited significant tubulo-interstitial injury and fibrosis and heavy inflammatory cell infiltration which were significantly improved with high resistant starch diet (Upper panel). Bar graphs depicting tubulointerstitial injury scores in the study groups (Lower panel).

Figure 2

Figure 2. Representative Western blots and group data depicting nuclear content of p65 active subunit of NF-κB and protein abundance of MCP-1, iNOS, COX-1, and COX-2 in the renal tissues of the normal control rats (n = 6) and CKD rats fed low fiber (n = 9) or high resistant starch supplemented diets (n = 9).

Data are means ± SE. *P<0.05, **P<0.01, ***P<0.001 VS CTL group, #P<0.05, ##P<0.01, ###P<0.001 VS CKD group.

Figure 3

Figure 3. Representative Western blots and group data depicting the NAD(P)H oxidase subunits (NOX-4, gp91phox) and nitrotyrosine abundance in the renal tissues of the normal control rats (n = 6) and CKD rats fed low fiber (n = 9) or high resistant starch supplemented diets (n = 9).

Data are means ± SE. *P<0.05, **P<0.01, ***P<0.001 VS CTL group, #P<0.05, ##P<0.01, ###P<0.001 VS CKD group.

Figure 4

Figure 4. Representative Western blots and group data depicting TGF-β, α-SM actin, and PAI-1 abundance in the renal tissues of the normal control rats (n = 6) and CKD rats fed low fiber (n = 9) or high resistant starch supplemented diets (n = 9).

Data are means ± SE. *P<0.05, **P<0.01, ***P<0.001 VS CTL group, #P<0.05, ##P<0.01, ###P<0.001 VS CKD group.

Figure 5

Figure 5. Representative Western blots and group data depicting nuclear translocation of Nrf2 and protein abundances of its downstream gene products, CuZn-SOD, catalase, heme oxygenase-1 (HO-1) and glutathione peroxidase (GPX) in the renal tissues of the normal control rats (n = 6) and CKD rats fed low fiber (n = 9) or resistant starch supplemented diets (n = 9).

*P<0.05, **P<0.01, ***P<0.001 VS CTL group, #P<0.05, ##P<0.01, ###P<0.001 VS CKD group.

Figure 6

Figure 6. Representative Western blots and group data depicting protein abundances of claudin-1 and occludin in the ascending colons of the normal control rats (n = 6) and CKD rats fed low fiber (n = 9) or resistant starch supplemented diets (n = 9).

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This study was supported in part by intramural USDA-ARS Project 5306-51530-019-00 (SHA) and the Danish Council for Strategic Research (RJM). USDA is an equal opportunity provider and employer. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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