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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Springer
2019
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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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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 |
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Intestinal permeability Microbiota Intestinal epithelium Arsenite Intestinal permeability Microbiota Intestinal epithelium Arsenite |
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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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