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Vitamin A Ameliorated Irinotecan-Induced Diarrhea in a Piglet Model Involving Enteric Glia Modulation and Immune Cells Infiltration

Vitamin A (VA) and its metabolite, retinoic acid (RA), play important roles in modulating intestinal mucosal immunity, yet little is known about their regulatory effects on enteric nervous system function. The study aims to explore the protective effects of dietary VA on diarrhea in a piglet model i...

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Autores principales: Li, Meng, Huang, Yonggang, Jin, Huimin, Yuan, Daixiu, Huang, Ke, Wang, Jing, Tan, Bie, Yin, Yulong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9739613/
https://www.ncbi.nlm.nih.gov/pubmed/36501151
http://dx.doi.org/10.3390/nu14235120
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author Li, Meng
Huang, Yonggang
Jin, Huimin
Yuan, Daixiu
Huang, Ke
Wang, Jing
Tan, Bie
Yin, Yulong
author_facet Li, Meng
Huang, Yonggang
Jin, Huimin
Yuan, Daixiu
Huang, Ke
Wang, Jing
Tan, Bie
Yin, Yulong
author_sort Li, Meng
collection PubMed
description Vitamin A (VA) and its metabolite, retinoic acid (RA), play important roles in modulating intestinal mucosal immunity, yet little is known about their regulatory effects on enteric nervous system function. The study aims to explore the protective effects of dietary VA on diarrhea in a piglet model involving enteric glia and immune cell modulation. Twenty-eight weaned piglets were fed either the basal or VA (basal diet supplemented with 18,000 IU/kg VA) diet and with or without irinotecan (CPT-11) injection. CPT-11 induced increased diarrhea incidence, immune infiltration, and reactive enteric gliosis. A diet supplemented with 18,000 IU/kg VA ameliorated the adverse effects of CPT-11 on the gut barrier. VA reduced diarrhea incidence and attenuated enteric glial gliosis, immune cell infiltrations, and inflammatory responses of CPT-induced piglets. An in vitro experiment with 1 nmol/L RA showed direct protective effects on monocultures of enteric glial cells (EGCs) or macrophages in LPS-simulated inflammatory conditions. Furthermore, 1 ng/mL glial-derived neurotropic factors (GDNF) could inhibit M1-macrophage polarization and pro-inflammatory cytokines production. In summary, VA exerted protective effects on the intestinal barrier by modulating enteric glia and immune cells, perhaps enhancing epithelial recovery under CPT-11 challenge. Our study demonstrated that RA signaling might promote the roles of enteric glia in intestinal immunity and tissue repair, which provided a reference for the VA supplementation of patient diets.
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spelling pubmed-97396132022-12-11 Vitamin A Ameliorated Irinotecan-Induced Diarrhea in a Piglet Model Involving Enteric Glia Modulation and Immune Cells Infiltration Li, Meng Huang, Yonggang Jin, Huimin Yuan, Daixiu Huang, Ke Wang, Jing Tan, Bie Yin, Yulong Nutrients Article Vitamin A (VA) and its metabolite, retinoic acid (RA), play important roles in modulating intestinal mucosal immunity, yet little is known about their regulatory effects on enteric nervous system function. The study aims to explore the protective effects of dietary VA on diarrhea in a piglet model involving enteric glia and immune cell modulation. Twenty-eight weaned piglets were fed either the basal or VA (basal diet supplemented with 18,000 IU/kg VA) diet and with or without irinotecan (CPT-11) injection. CPT-11 induced increased diarrhea incidence, immune infiltration, and reactive enteric gliosis. A diet supplemented with 18,000 IU/kg VA ameliorated the adverse effects of CPT-11 on the gut barrier. VA reduced diarrhea incidence and attenuated enteric glial gliosis, immune cell infiltrations, and inflammatory responses of CPT-induced piglets. An in vitro experiment with 1 nmol/L RA showed direct protective effects on monocultures of enteric glial cells (EGCs) or macrophages in LPS-simulated inflammatory conditions. Furthermore, 1 ng/mL glial-derived neurotropic factors (GDNF) could inhibit M1-macrophage polarization and pro-inflammatory cytokines production. In summary, VA exerted protective effects on the intestinal barrier by modulating enteric glia and immune cells, perhaps enhancing epithelial recovery under CPT-11 challenge. Our study demonstrated that RA signaling might promote the roles of enteric glia in intestinal immunity and tissue repair, which provided a reference for the VA supplementation of patient diets. MDPI 2022-12-02 /pmc/articles/PMC9739613/ /pubmed/36501151 http://dx.doi.org/10.3390/nu14235120 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Li, Meng
Huang, Yonggang
Jin, Huimin
Yuan, Daixiu
Huang, Ke
Wang, Jing
Tan, Bie
Yin, Yulong
Vitamin A Ameliorated Irinotecan-Induced Diarrhea in a Piglet Model Involving Enteric Glia Modulation and Immune Cells Infiltration
title Vitamin A Ameliorated Irinotecan-Induced Diarrhea in a Piglet Model Involving Enteric Glia Modulation and Immune Cells Infiltration
title_full Vitamin A Ameliorated Irinotecan-Induced Diarrhea in a Piglet Model Involving Enteric Glia Modulation and Immune Cells Infiltration
title_fullStr Vitamin A Ameliorated Irinotecan-Induced Diarrhea in a Piglet Model Involving Enteric Glia Modulation and Immune Cells Infiltration
title_full_unstemmed Vitamin A Ameliorated Irinotecan-Induced Diarrhea in a Piglet Model Involving Enteric Glia Modulation and Immune Cells Infiltration
title_short Vitamin A Ameliorated Irinotecan-Induced Diarrhea in a Piglet Model Involving Enteric Glia Modulation and Immune Cells Infiltration
title_sort vitamin a ameliorated irinotecan-induced diarrhea in a piglet model involving enteric glia modulation and immune cells infiltration
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9739613/
https://www.ncbi.nlm.nih.gov/pubmed/36501151
http://dx.doi.org/10.3390/nu14235120
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