Oral Activated Charcoal Adsorbent (AST-120) Ameliorates Chronic Kidney Disease-Induced Intestinal Epithelial Barrier Disruption

被引:102
作者
Vaziri, Nosratola D. [1 ]
Yuan, Jun [1 ]
Khazaeli, Mahyar [1 ]
Masuda, Yuichi [2 ]
Ichii, Hirohito [2 ]
Liu, Shuman [1 ]
机构
[1] Univ Calif Irvine, Div Nephrol & Hypertens, Irvine, CA USA
[2] Univ Calif Irvine, Dept Surg, Irvine, CA 92717 USA
关键词
Epithelial tight junction; Endotoxin; Activated charcoal; End-stage renal disease; Uremia; SIZED POLYETHYLENE-GLYCOLS; CHRONIC-RENAL-FAILURE; HEMODIALYSIS-PATIENTS; MICROBIAL-FLORA; UREMIC SOLUTES; TIGHT JUNCTION; INFLAMMATION; RATS; CKD; ASSOCIATIONS;
D O I
10.1159/000351171
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Background: Chronic kidney disease (CKD) impairs intestinal barrier function which by allowing influx of noxious products causes systemic inflammation. We have recently shown that intestinal barrier dysfunction in CKD is due to degradation of epithelial tight junction (TJ) which is, in part, mediated by influx of urea and its conversion to ammonia by microbial urease. We hypothesized that by adsorbing urea and urea-derived ammonia, oral activated charcoal (AST-120) may ameliorate CKD-induced intestinal epithelial barrier disruption and systemic inflammation. Methods: Rats were randomized to the CKD or control groups. The CKD group was fed a chow containing 0.7% adenine for 2 weeks. They were then randomized to receive a chow with or without AST-120 (4 g/kg/day) for 2 weeks. Rats consuming regular diet served as controls. Animals were then euthanized, colons were removed and processed for Western blot and immunohistology, and plasma was used to measure endotoxin and oxidative and inflammatory markers. Results: Compared with the controls, the untreated CKD rats showed elevated plasma endotoxin, IL-6, TNF-alpha, MCP-1, CINC-3, L-selectin, ICAM-1, and malondialdehyde, and depletions of colonic epithelial TJ proteins, claudin-1, occludin, and ZO1. Administration of AST-120 resulted in partial restoration of the epithelial TJ proteins and reduction in plasma endotoxin and markers of oxidative stress and inflammation. Conclusions: CKD animals exhibited depletion of the key protein constituents of the colonic epithelial TJ which was associated with systemic inflammation, oxidative stress and endotoxemia. Administration of AST-120 attenuated uremia-induced disruption of colonic epithelial TJ and the associated endotoxemia, oxidative stress and inflammation. Copyright (c) 2013 S. Karger AG, Basel
引用
收藏
页码:518 / 525
页数:8
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