Instituto de Agroquímica y Tecnología de Alimentos (IATA-CSIC), Calle Agustín Escardino 7, 46980 - Paterna, Valencia, Spain.
Metallomics. 2019 Aug 1;11(8):1411-1418. doi: 10.1039/c9mt00144a. Epub 2019 Jul 17.
Inorganic arsenic (As) is the most toxic form of As found in food and water. Gastrointestinal disorders have been reported in populations chronically exposed to this arsenical form or to one of its metabolites; however, studies to determine the mechanisms of inorganic As toxicity at the intestinal level are scarce. The aim of this study is to determine the mechanisms of toxicity of inorganic As [As(iii) and As(v)] on intestinal epithelial cells. For this purpose, two human intestinal cell models were used: non-transformed colon epithelial cells (NCM460) and epithelial cells from a colorectal adenocarcinoma (Caco-2). Exposure to As(iii) and As(v) generates an increase in the release of the pro-inflammatory cytokine IL-8 (57-1135%) and an increase in the generation of reactive oxygen and/or nitrogen species (130-340%) in both cell lines. This pro-inflammatory and pro-oxidant response may be responsible for the structural and functional modifications demonstrated in the monolayers formed by both cell types. Treatments with As(iii) and As(v) produce a redistribution of zonula occludens 1 and a reduction in the expression of claudin 1, tight junction proteins that participate in maintaining the structure of the epithelium. All these toxic effects are finally translated into a loss of the barrier function of intestinal monolayers.
无机砷（As）是食物和水中存在的最具毒性的砷形式。长期接触这种砷化物或其代谢物的人群会出现胃肠道紊乱；然而，目前对于确定无机砷在肠道水平的毒性机制的研究还很缺乏。本研究旨在确定无机砷 [As(iii) 和 As(v)] 对肠道上皮细胞的毒性机制。为此，我们使用了两种人类肠道细胞模型：非转化结肠上皮细胞（NCM460）和结直肠腺癌细胞（Caco-2）。暴露于 As(iii) 和 As(v) 会导致两种细胞系中促炎细胞因子 IL-8 的释放增加（57-1135%），活性氧和/或氮物种的生成增加（130-340%）。这种促炎和促氧化反应可能是两种细胞类型形成的单层中表现出的结构和功能改变的原因。As(iii) 和 As(v) 的处理会导致紧密连接蛋白 zonula occludens 1 的重新分布和 claudin 1 的表达减少，这些紧密连接蛋白参与维持上皮结构。所有这些毒性作用最终导致肠道单层屏障功能的丧失。
