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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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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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. |
format | Online Article Text |
id | pubmed-7880462 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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