Oral activated charcoal adsorbent (AST-120) ameliorates chronic kidney disease-induced intestinal epithelial barrier disruption.
Oral activated charcoal adsorbent (AST-120) ameliorates chronic kidney disease-induced intestinal epithelial barrier disruption.
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DOI：
10.1159/000351171
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发表时间：
2013
影响因子：
4.2
通讯作者：
Liu S
中科院分区：
文献类型：
--
作者：
Vaziri ND;Yuan J;Khazaeli M;Masuda Y;Ichii H;Liu S
CKD损害肠道屏障功能，通过允许有害产物流入导致全身炎症。我们最近发现，肠屏障功能障碍的CKD是由于上皮细胞紧密连接（TJ）的降解，这是，在一定程度上，介导的流入尿素和微生物尿素酶转化为氨。我们假设，通过吸附尿素和尿素衍生的氨，口服活性炭（AST-120）可以改善CKD诱导的肠上皮屏障破坏和全身炎症。将大鼠随机分为CKD组和对照组。CKD组喂饲含0.7%腺嘌呤的饲料2周。然后将其随机接受含或不含AST-120（4 g/kg/天）的食物，持续2周。正常饮食的大鼠作为对照组。然后将动物安乐死，取出结肠并进行蛋白质印迹和免疫组织学处理，并使用血浆测量内毒素以及氧化和炎症标志物。与对照组相比，未治疗的CKD大鼠显示血浆内毒素、IL-6、TNFα、MCP-1、CINC-3、L-选择素、ICAM-1和丙二醛升高，结肠上皮TJ蛋白（claudin-1、occludin和ZO 1）减少。AST-120的给药导致上皮TJ蛋白的部分恢复和血浆内毒素以及氧化应激和炎症标志物的减少。CKD动物表现出结肠上皮TJ的关键蛋白组分的耗竭，这与全身性炎症、氧化应激和内毒素血症相关。AST-120的给药减弱了尿毒症诱导的结肠上皮TJ破坏以及相关的内毒素血症、氧化应激和炎症。
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. 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. Compared with the controls the untreated CKD rats showed elevated plasma endotoxin, IL-6, TNFα, 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. 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.
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影响因子：
19.6
作者：
Vaziri, Nosratola D.;Wong, Jakk;Andersen, Gary L.
通讯作者：
Andersen, Gary L.
影响因子：
13.6
作者：
Aronov, Pavel A.;Luo, Frank J. -G.;Meyer, Timothy W.
通讯作者：
Meyer, Timothy W.
影响因子：
4.2
作者：
Vaziri ND;Yuan J;Norris K
通讯作者：
Norris K
影响因子：
6.1
作者：
Goncalves, Simone;Pecoits Filho, Roberto;Riella, Miguel C.
通讯作者：
Riella, Miguel C.
影响因子：
24.5
作者：
MAGNUSSON, M;MAGNUSSON, KE;DENNEBERG, T
通讯作者：
DENNEBERG, T