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亚慢性暴露于无机砷对肠上皮结构和功能的影响。

Effect of subchronic exposure to inorganic arsenic on the structure and function of the intestinal epithelium.

作者信息

Chiocchetti G M, Vélez D, Devesa V

机构信息

Instituto de Agroquímica y Tecnología de Alimentos (IATA-CSIC), Calle Agustín Escardino 7, 46980, Paterna, Valencia, Spain.

Instituto de Agroquímica y Tecnología de Alimentos (IATA-CSIC), Calle Agustín Escardino 7, 46980, Paterna, Valencia, Spain.

出版信息

Toxicol Lett. 2018 Apr;286:80-88. doi: 10.1016/j.toxlet.2018.01.011. Epub 2018 Jan 31.

Abstract

Inorganic arsenic (As), the most toxic form of As found in water and food, is considered a human carcinogen. Numerous studies show its systemic toxicity, describing pathologies associated with chronic exposure. The main pathway of exposure to inorganic As is oral, but many of the events that occur during its passage through the gastrointestinal tract are unknown. This study evaluates the effect of subchronic exposure to inorganic As [As(III): 0.025-0.1 mg/L; As(V): 0.25-1 mg/L, up to 21 days] on the intestinal epithelium, using Caco-2 cells as in vitro model. Inorganic As produces a pro-inflammatory response throughout the exposure time, with an increase in IL-8 release (up to 488%). It also causes changes in the program of cell proliferation and differentiation, which leads to impairment of the cell repair process. In addition, subchronic exposure affects the epithelial structure, causing loss of microvilli, fundamental structures in the processes of intestinal absorption and digestion. Moreover, the exposure affects the epithelial barrier function, evidenced by an increase of Lucifer Yellow transport (103-199%). Therefore, it can be concluded that subchronic exposure to inorganic As can alter intestinal homeostasis, affecting the mucosal layer, which performs the most important functions of the intestinal wall.

摘要

无机砷(As)是在水和食物中发现的毒性最强的砷形态,被认为是一种人类致癌物。大量研究表明其具有全身毒性,描述了与长期接触相关的病理情况。接触无机砷的主要途径是经口摄入,但在其通过胃肠道的过程中发生的许多事件尚不清楚。本研究使用Caco-2细胞作为体外模型,评估亚慢性接触无机砷[三价砷(As(III)):0.025 - 0.1毫克/升;五价砷(As(V)):0.25 - 1毫克/升,长达21天]对肠上皮的影响。无机砷在整个接触期间都会产生促炎反应,白细胞介素-8(IL-8)释放增加(高达488%)。它还会导致细胞增殖和分化程序发生变化,进而导致细胞修复过程受损。此外,亚慢性接触会影响上皮结构,导致微绒毛丧失,而微绒毛是肠道吸收和消化过程中的基本结构。而且,这种接触会影响上皮屏障功能,荧光素黄转运增加(103 - 199%)就证明了这一点。因此,可以得出结论,亚慢性接触无机砷会改变肠道内环境稳定,影响执行肠壁最重要功能的黏膜层。

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