In vivo evaluation of the effect of arsenite on the intestinal epithelium and associated microbiota in mice

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-1β, 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.

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Main Authors: Chiocchetti, Gabriela M., Domene, Adrián, Kühl, Anja A., Zúñiga, Manuel, Vélez, Dinoraz, Devesa, Vicenta, Monedero, Vicente
Other Authors: Ministerio de Economía y Competitividad (España)
Format: artículo biblioteca
Published: Springer 2019
Subjects:Intestinal permeability, Microbiota, Intestinal epithelium, Arsenite,
Online Access:http://hdl.handle.net/10261/197437
http://dx.doi.org/10.13039/501100003329
http://dx.doi.org/10.13039/501100002322
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spelling dig-iata-es-10261-1974372022-01-20T12:37:18Z In vivo evaluation of the effect of arsenite on the intestinal epithelium and associated microbiota in mice Chiocchetti, Gabriela M. Domene, Adrián Kühl, Anja A. Zúñiga, Manuel Vélez, Dinoraz Devesa, Vicenta Monedero, Vicente Ministerio de Economía y Competitividad (España) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Brasil) Intestinal permeability Microbiota Intestinal epithelium Arsenite 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-1β, 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. This work was supported by the Spanish Ministry of Science, Innovation and Universities (AGL2015-68920-R), for which the authors are deeply indebted. Gabriela M. Chiocchetti received a fellowship from the Brazilian Government (CAPES BEX1086/14-6). We thank M.C. Collado, C. Alcántara, M. Selma, M. Dzidic and A. Boix for their advice in metagenome analyses. We also thank Inmaculada Noguera, from the Animal Production Service from the University of Valencia, for her assistance in the animal experiments. Peer Reviewed 2020-01-07T10:47:33Z 2020-01-07T10:47:33Z 2019 2020-01-07T10:47:34Z artículo http://purl.org/coar/resource_type/c_6501 doi: 10.1007/s00204-019-02510-w issn: 1432-0738 Archives of Toxicology 93 (8):2127-2139 (2019) http://hdl.handle.net/10261/197437 10.1007/s00204-019-02510-w http://dx.doi.org/10.13039/501100003329 http://dx.doi.org/10.13039/501100002322 #PLACEHOLDER_PARENT_METADATA_VALUE# info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/AGL2015-68920-R Postprint Sí open Springer
institution IATA ES
collection DSpace
country España
countrycode ES
component Bibliográfico
access En linea
databasecode dig-iata-es
tag biblioteca
region Europa del Sur
libraryname Biblioteca del IATA España
topic Intestinal permeability
Microbiota
Intestinal epithelium
Arsenite
Intestinal permeability
Microbiota
Intestinal epithelium
Arsenite
spellingShingle Intestinal permeability
Microbiota
Intestinal epithelium
Arsenite
Intestinal permeability
Microbiota
Intestinal epithelium
Arsenite
Chiocchetti, Gabriela M.
Domene, Adrián
Kühl, Anja A.
Zúñiga, Manuel
Vélez, Dinoraz
Devesa, Vicenta
Monedero, Vicente
In vivo evaluation of the effect of arsenite on the intestinal epithelium and associated microbiota in mice
description 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-1β, 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.
author2 Ministerio de Economía y Competitividad (España)
author_facet Ministerio de Economía y Competitividad (España)
Chiocchetti, Gabriela M.
Domene, Adrián
Kühl, Anja A.
Zúñiga, Manuel
Vélez, Dinoraz
Devesa, Vicenta
Monedero, Vicente
format artículo
topic_facet Intestinal permeability
Microbiota
Intestinal epithelium
Arsenite
author Chiocchetti, Gabriela M.
Domene, Adrián
Kühl, Anja A.
Zúñiga, Manuel
Vélez, Dinoraz
Devesa, Vicenta
Monedero, Vicente
author_sort Chiocchetti, Gabriela M.
title In vivo evaluation of the effect of arsenite on the intestinal epithelium and associated microbiota in mice
title_short In vivo evaluation of the effect of arsenite on the intestinal epithelium and associated microbiota in mice
title_full In vivo evaluation of the effect of arsenite on the intestinal epithelium and associated microbiota in mice
title_fullStr In vivo evaluation of the effect of arsenite on the intestinal epithelium and associated microbiota in mice
title_full_unstemmed In vivo evaluation of the effect of arsenite on the intestinal epithelium and associated microbiota in mice
title_sort in vivo evaluation of the effect of arsenite on the intestinal epithelium and associated microbiota in mice
publisher Springer
publishDate 2019
url http://hdl.handle.net/10261/197437
http://dx.doi.org/10.13039/501100003329
http://dx.doi.org/10.13039/501100002322
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