Location: Obesity and Metabolism ResearchTitle: High amylose resistant starch diet ameliorates oxidative stress, inflammation, and progression of chronic kidney disease (CKD)
|LIU, SHUMAN - University Of California|
|NAZER-TEHRANI, SOHRAB - University Of California|
|FARZANEH, SEYED - University Of California|
|LAU, W - University Of California|
|KHAZAELI, MAHYAR - University Of California|
|KIEFFER, DOROTHY - University Of California|
|MARTIN, ROY - University Of California|
|VAZIRI, N - University Of California|
Submitted to: PLoS ONE
Publication Type: Abstract Only
Publication Acceptance Date: 12/9/2014
Publication Date: 12/9/2014
Citation: Liu, S., Nazer-Tehrani, S., Farzaneh, S.H., Lau, W.L., Khazaeli, M., Adams, S.H., Kieffer, D.A., Martin, R., Vaziri, N.D. 2014. High amylose resistant starch diet ameliorates oxidative stress, inflammation, and progression of chronic kidney disease (CKD). PLoS One. 9(12):e114881. DOI: 10.1371/journal.pone.0114881.
Technical Abstract: Patients with advanced CKD exhibit profound changes in the composition and function of the gut microbiome. This is, in part, mediated by: I- heavy influx of urea in the intestinal tract leading to the dominance of urease-possessing bacteria and II- dietary restriction of potassium-rich fruits and vegetables which are the main source of dietary fiber. This leads to the contraction of bacterial species capable of converting dietary fiber to short chain fatty acids (SCFA). Conversion of urea to NH3 & NH4OH by urease-possessing bacteria leads to erosion of the intestinal epithelial tight junction which evokes inflammation by facilitating translocation of endotoxin and bacterial components into the circulation. This is compounded by the reduction of SCFA which are essential for growth and survival of the anti-inflammatory regulatory T lymphocytes. We therefore tested the hypothesis that dietary soluble fiber supplementation may attenuate oxidative stress, inflammation and CKD progression. Methods- SD rats were fed a rat chow containing 0.7% adenine for 2 weeks to induce chronic interstitial nephropathy (CKD). They were then placed on either a regular diet or a diet containing 30% high amylose-resistant starch (HAMRS2) for 3 weeks. Rats consuming regular diet served as controls. The rats were then euthanized and kidney tissue harvested and processed for histological and Western blot analyses. Results- Compared with the controls, the untreated CKD rats exhibited severe polyuria, impaired urinary concentration capacity, reduced creatinine clearance, intense renal interstitial fibrosis and mononuclear leukocyte infiltration, and tubular atrophy and dilatation. This was associated with activation (nuclear translocation) of NFkB, upregulation of pro-inflammatory (MCP-1, COX-1, COX-2, iNOS), pro-oxidant (gp91, and NOX-4) and pro-fibrotic (PAI-1, TGF-b, and alpha-SM actin) molecules; impaired nuclear translocation of transcription factor, Nrf2, and down-regulation of its key antioxidant and cytoprotective target gene products (catalase, superoxide dismutase, glutathione peroxidase and heme oxigenase-1), and down-regulation of eNOS. Consumption of the high amylose-resistant starch diet resulted in significant improvement of creatinine clearance, polyuria, urine concentrating capacity, interstitial fibrosis, inflammation, tubular damage and attenuation of the upregulation of oxidative, inflammatory, and fibrotic pathways and partial restoration of Nrf2 activity. Conclusions- Consumption of diet high in resistant starch retards CKD progression, attenuates oxidative stress and inflammation, and improves endogenous cytoprotective pathways in experimental animals. Clinical studies are needed to explore the impact of high fiber diet in patients with CKD.