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Alteration of oxidative-stress and related marker levels in mouse colonic tissues and fecal microbiota structures with chronic ethanol administration: Implications for the pathogenesis of ethanol-related colorectal cancer

Chronic ethanol consumption is a risk factor for colorectal cancer, and ethanol-induced reactive oxygen species have been suggested to play important roles in the pathogenesis of ethanol-related colorectal cancer (ER-CRC). In this study, the effects of 10-week chronic administration of ethanol on th...

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Autores principales: Ohira, Hideo, Tsuruya, Atsuki, Oikawa, Daiki, Nakagawa, Wao, Mamoto, Rie, Hattori, Masahira, Waki, Toshiyuki, Takahashi, Seiji, Fujioka, Yoshio, Nakayama, Toru
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880462/
https://www.ncbi.nlm.nih.gov/pubmed/33577585
http://dx.doi.org/10.1371/journal.pone.0246580
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author Ohira, Hideo
Tsuruya, Atsuki
Oikawa, Daiki
Nakagawa, Wao
Mamoto, Rie
Hattori, Masahira
Waki, Toshiyuki
Takahashi, Seiji
Fujioka, Yoshio
Nakayama, Toru
author_facet Ohira, Hideo
Tsuruya, Atsuki
Oikawa, Daiki
Nakagawa, Wao
Mamoto, Rie
Hattori, Masahira
Waki, Toshiyuki
Takahashi, Seiji
Fujioka, Yoshio
Nakayama, Toru
author_sort Ohira, Hideo
collection PubMed
description Chronic ethanol consumption is a risk factor for colorectal cancer, and ethanol-induced reactive oxygen species have been suggested to play important roles in the pathogenesis of ethanol-related colorectal cancer (ER-CRC). In this study, the effects of 10-week chronic administration of ethanol on the colonic levels of oxidative stress and advance glycation end product (AGE) levels, as well as fecal microbiota structures, were examined in a mouse model. Chronic oral administration of ethanol in mice (1.0 mL of 1.5% or 5.0% ethanol (v/v) per day per mouse, up to 10 weeks) resulted in the elevation of colonic levels of oxidative stress markers (such as 8-hydroxy-2’-deoxyguanosine and 4-hydroxynonenal) compared to control mice, and this was consistently accompanied by elevated levels of inflammation-associated cytokines and immune cells (Th17 and macrophages) and a decreased level of regulatory T (Treg) cells to produce colonic lesions. It also resulted in an alteration of mouse fecal microbiota structures, reminiscent of the alterations observed in human inflammatory bowel disease, and this appeared to be consistent with the proposed sustained generation of oxidative stress in the colonic environment during chronic ethanol consumption. Moreover, the first experimental evidence that chronic ethanol administration results in elevated levels of advanced glycation end products (AGEs) and their receptors (RAGE) in the colonic tissues in mice is also shown, implying enhanced RAGE-mediated signaling with chronic ethanol administration. The RAGE-mediated signaling pathway has thus far been implicated as a link between the accumulation of AGEs and the development of many types of chronic colitis and cancers. Thus, enhancement of this pathway likely exacerbates the ethanol-induced inflammatory states of colonic tissues and might at least partly contribute to the pathogenesis of ER-CRC.
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spelling pubmed-78804622021-02-19 Alteration of oxidative-stress and related marker levels in mouse colonic tissues and fecal microbiota structures with chronic ethanol administration: Implications for the pathogenesis of ethanol-related colorectal cancer Ohira, Hideo Tsuruya, Atsuki Oikawa, Daiki Nakagawa, Wao Mamoto, Rie Hattori, Masahira Waki, Toshiyuki Takahashi, Seiji Fujioka, Yoshio Nakayama, Toru PLoS One Research Article Chronic ethanol consumption is a risk factor for colorectal cancer, and ethanol-induced reactive oxygen species have been suggested to play important roles in the pathogenesis of ethanol-related colorectal cancer (ER-CRC). In this study, the effects of 10-week chronic administration of ethanol on the colonic levels of oxidative stress and advance glycation end product (AGE) levels, as well as fecal microbiota structures, were examined in a mouse model. Chronic oral administration of ethanol in mice (1.0 mL of 1.5% or 5.0% ethanol (v/v) per day per mouse, up to 10 weeks) resulted in the elevation of colonic levels of oxidative stress markers (such as 8-hydroxy-2’-deoxyguanosine and 4-hydroxynonenal) compared to control mice, and this was consistently accompanied by elevated levels of inflammation-associated cytokines and immune cells (Th17 and macrophages) and a decreased level of regulatory T (Treg) cells to produce colonic lesions. It also resulted in an alteration of mouse fecal microbiota structures, reminiscent of the alterations observed in human inflammatory bowel disease, and this appeared to be consistent with the proposed sustained generation of oxidative stress in the colonic environment during chronic ethanol consumption. Moreover, the first experimental evidence that chronic ethanol administration results in elevated levels of advanced glycation end products (AGEs) and their receptors (RAGE) in the colonic tissues in mice is also shown, implying enhanced RAGE-mediated signaling with chronic ethanol administration. The RAGE-mediated signaling pathway has thus far been implicated as a link between the accumulation of AGEs and the development of many types of chronic colitis and cancers. Thus, enhancement of this pathway likely exacerbates the ethanol-induced inflammatory states of colonic tissues and might at least partly contribute to the pathogenesis of ER-CRC. Public Library of Science 2021-02-12 /pmc/articles/PMC7880462/ /pubmed/33577585 http://dx.doi.org/10.1371/journal.pone.0246580 Text en © 2021 Ohira et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Ohira, Hideo
Tsuruya, Atsuki
Oikawa, Daiki
Nakagawa, Wao
Mamoto, Rie
Hattori, Masahira
Waki, Toshiyuki
Takahashi, Seiji
Fujioka, Yoshio
Nakayama, Toru
Alteration of oxidative-stress and related marker levels in mouse colonic tissues and fecal microbiota structures with chronic ethanol administration: Implications for the pathogenesis of ethanol-related colorectal cancer
title Alteration of oxidative-stress and related marker levels in mouse colonic tissues and fecal microbiota structures with chronic ethanol administration: Implications for the pathogenesis of ethanol-related colorectal cancer
title_full Alteration of oxidative-stress and related marker levels in mouse colonic tissues and fecal microbiota structures with chronic ethanol administration: Implications for the pathogenesis of ethanol-related colorectal cancer
title_fullStr Alteration of oxidative-stress and related marker levels in mouse colonic tissues and fecal microbiota structures with chronic ethanol administration: Implications for the pathogenesis of ethanol-related colorectal cancer
title_full_unstemmed Alteration of oxidative-stress and related marker levels in mouse colonic tissues and fecal microbiota structures with chronic ethanol administration: Implications for the pathogenesis of ethanol-related colorectal cancer
title_short Alteration of oxidative-stress and related marker levels in mouse colonic tissues and fecal microbiota structures with chronic ethanol administration: Implications for the pathogenesis of ethanol-related colorectal cancer
title_sort alteration of oxidative-stress and related marker levels in mouse colonic tissues and fecal microbiota structures with chronic ethanol administration: implications for the pathogenesis of ethanol-related colorectal cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880462/
https://www.ncbi.nlm.nih.gov/pubmed/33577585
http://dx.doi.org/10.1371/journal.pone.0246580
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