Oral activated charcoal adsorbent (AST-120) ameliorates chronic kidney disease-induced intestinal epithelial barrier disruption.
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, mediate...
| Publicado en: | American Journal of Nephrology Vol. 37; no. 6; pp. 518 - 526 |
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| Autores principales: | , , , , , |
| Formato: | research Journal Article |
| Publicado: |
Karger AG
Jun2013
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=104189375&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 104189375 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 02508095 8BL jtl: American Journal of Nephrology issn: 02508095 maglogo: N pubinfo: dt: Jun2013 vid: 37 iid: 6 pid: 2485 pub: Karger AG artinfo: ui: 104189375 NLM23689670 2012175774 10.1159/000351171 NLM23689670 PMC3777856 104189375 ppf: 518 ppct: 8 formats: tig: atl: Oral activated charcoal adsorbent (AST-120) ameliorates chronic kidney disease-induced intestinal epithelial barrier disruption. aug: au: Vaziri, Nosratola D Yuan, Jun Khazaeli, Mahyar Masuda, Yuichi Ichii, Hirohito Liu, Shuman affil: Division of Nephrology and Hypertension, University of California, Irvine, Calif., USA. sug: subj: Carbon Pharmacodynamics Cell Membrane Drug Effects Gastrointestinal Agents Pharmacodynamics Intestinal Diseases Etiology Intestinal Mucosa Drug Effects Oxides Pharmacodynamics Renal Insufficiency Complications Administration, Oral Adsorption Animal Studies Cell Membrane Cell Membrane Metabolism Endotoxemia Endotoxins Metabolism Inflammation Mediators Metabolism Inflammation Complications Intestinal Diseases Intestinal Diseases Immunology Intestinal Mucosa Immunology Intestinal Mucosa Metabolism Male Permeability Rats Urea Male ab: 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. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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