title: Oral activated charcoal adsorbent (AST-120) ameliorates chronic kidney disease-induced intestinal epithelial barrier disruption.
abstract: 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-α, 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.
authors.affiliation: Division of Nephrology and Hypertension, University of California, Irvine, Calif., USA. ndvaziri@uci.edu
authors.forename: Nosratola D
authors.initials: ND
authors.lastname: Vaziri
authors.forename: Jun
authors.initials: J
authors.lastname: Yuan
authors.forename: Mahyar
authors.initials: M
authors.lastname: Khazaeli
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Masuda
authors.forename: Hirohito
authors.initials: H
authors.lastname: Ichii
authors.forename: Shuman
authors.initials: S
authors.lastname: Liu
mesh_terms: D000284:Administration, Oral; D000327:Adsorption; D000818:Animals; D002244:Carbon / Q000494:pharmacology*; D062445:Claudin-1 / Q000187:drug effects / Q000378:metabolism; D019446:Endotoxemia / Q000150:complications; D004731:Endotoxins / Q000378:metabolism; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D007249:Inflammation; D018836:Inflammation Mediators / Q000276:immunology; D007410:Intestinal Diseases / Q000209:etiology* / Q000276:immunology / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008297:Male; D062793:Occludin / Q000187:drug effects / Q000378:metabolism; D010087:Oxides / Q000494:pharmacology*; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D051436:Renal Insufficiency, Chronic / Q000150:complications*; D019108:Tight Junctions / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D014508:Urea / Q000276:immunology / Q000378:metabolism; D062826:Zonula Occludens-1 Protein / Q000187:drug effects / Q000378:metabolism
chemical_list: D062445:Claudin-1; C568114:Cldn1 protein, rat; D004731:Endotoxins; D005765:Gastrointestinal Agents; D018836:Inflammation Mediators; D062793:Occludin; C568987:Ocln protein, rat; D010087:Oxides; C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein; D002244:Carbon; D014508:Urea; C040896:AST 120