In vivo evaluation of the effect of arsenite on the intestinal epithelium and associated microbiota in mice
In vivo evaluation of the effect of arsenite on the intestinal epithelium and associated microbiota in mice
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DOI：
10.1007/s00204-019-02510-w
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发表时间：
2019-08-01
影响因子：
6.1
通讯作者：
Monedero, Vicente
中科院分区：
文献类型：
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作者：
Chiocchetti, Gabriela M.;Domene, Adrian;Monedero, Vicente
长期接触无机砷（As）[As（III）+ As（V）]影响数百万人，增加了某些癌症和其他非致癌性疾病的发病率。虽然口服途径是主要的暴露形式，但尚未进行体内研究来验证该类金属的肠道毒性。本研究的目的是进行体内评价的肠道毒性的无机砷，通过饮用水暴露于不同浓度的As（III）（20，50和80毫克/升）2个月的雌性BALB/c小鼠。在浓度等于或大于50 mg/L时，观察到氧和/或氮反应性物质以及促炎细胞因子（IL-1 β、IL-2、IL-6）的基因和蛋白表达增加。这些变化伴随着肠道微生物在多样性和全球组成方面的深刻重塑，这可能是As（III）毒性作用的基础或加剧As（III）毒性作用。组织学研究表明，在最高给药剂量下，粘膜和粘膜下层存在中度炎症，伴有隐窝增生。此外，所有的治疗与As（III）导致Muc 2的表达减少，这编码的主要组成部分之一的肠粘液层。所述效应与在等于或大于50 mg/L的浓度下观察到的肠通透性增加一致，表明屏障功能丧失。
Chronic exposure to inorganic arsenic (As) [As(III) + As(V)], which affects millions of people, increases the incidence of some kinds of cancer and other non-carcinogenic pathologies. Although the oral pathway is the main form of exposure, in vivo studies have not been conducted to verify the intestinal toxicity of this metalloid. The aim of this study is to perform an in vivo evaluation of the intestinal toxicity of inorganic As, using female BALB/c mice exposed through drinking water to various concentrations of As(III) (20, 50, and 80 mg/L) for 2 months. An increase was observed in oxygen and/or nitrogen reactive species, and in gene and protein expression of pro-inflammatory cytokines (IL-1 beta, IL-2, IL-6) at concentrations equal to or greater than 50 mg/L. These changes were accompanied by a profound remodeling of the intestinal microbial profile in terms of diversity and global composition, which could be at the basis or exacerbate As(III) toxic effects. The histological study showed that there was moderate inflammation of the mucosa and submucosa, accompanied by hyperplasia of crypts at the highest administered dose. In addition, all the treatments with As(III) resulted in a decreased expression of Muc2, which encodes one of the main components of the intestinal layer of mucus. The effects described are compatible with the increased intestinal permeability observed at concentrations equal to or greater than 50 mg/L, indicative of loss of barrier function.