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5-Aminolevulinic Acid as a Novel Therapeutic for Inflammatory Bowel Disease
5-Aminolevulinic acid (5-ALA) is a naturally occurring nonprotein amino acid licensed as an optical imaging agent for the treatment of gliomas. In recent years, 5-ALA has been shown to possess anti-inflammatory and immunoregulatory properties through upregulation of heme oxygenase-1 via enhancement...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160866/ https://www.ncbi.nlm.nih.gov/pubmed/34065300 http://dx.doi.org/10.3390/biomedicines9050578 |
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author | Yadav, Vipul Mai, Yang McCoubrey, Laura E. Wada, Yasufumi Tomioka, Motoyasu Kawata, Satofumi Charde, Shrikant Basit, Abdul W. |
author_facet | Yadav, Vipul Mai, Yang McCoubrey, Laura E. Wada, Yasufumi Tomioka, Motoyasu Kawata, Satofumi Charde, Shrikant Basit, Abdul W. |
author_sort | Yadav, Vipul |
collection | PubMed |
description | 5-Aminolevulinic acid (5-ALA) is a naturally occurring nonprotein amino acid licensed as an optical imaging agent for the treatment of gliomas. In recent years, 5-ALA has been shown to possess anti-inflammatory and immunoregulatory properties through upregulation of heme oxygenase-1 via enhancement of porphyrin, indicating that it may be beneficial for the treatment of inflammatory conditions. This study systematically examines 5-ALA for use in inflammatory bowel disease (IBD). Firstly, the ex vivo colonic stability and permeability of 5-ALA was assessed using human and mouse fluid and tissue. Secondly, the in vivo efficacy of 5-ALA, in the presence of sodium ferrous citrate, was investigated via the oral and intracolonic route in an acute DSS colitis mouse model of IBD. Results showed that 5-ALA was stable in mouse and human colon fluid, as well as in colon tissue. 5-ALA showed more tissue restricted pharmacokinetics when exposed to human colonic tissue. In vivo dosing demonstrated significantly improved colonic inflammation, increased local heme oxygenase-1 levels, and decreased concentrations of proinflammatory cytokines TNF-α, IL-6, and IL-1β in both plasma and colonic tissue. These effects were superior to that measured concurrently with established anti-inflammatory treatments, ciclosporin and 5-aminosalicylic acid (mesalazine). As such, 5-ALA represents a promising addition to the IBD armamentarium, with potential for targeted colonic delivery. |
format | Online Article Text |
id | pubmed-8160866 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-81608662021-05-29 5-Aminolevulinic Acid as a Novel Therapeutic for Inflammatory Bowel Disease Yadav, Vipul Mai, Yang McCoubrey, Laura E. Wada, Yasufumi Tomioka, Motoyasu Kawata, Satofumi Charde, Shrikant Basit, Abdul W. Biomedicines Article 5-Aminolevulinic acid (5-ALA) is a naturally occurring nonprotein amino acid licensed as an optical imaging agent for the treatment of gliomas. In recent years, 5-ALA has been shown to possess anti-inflammatory and immunoregulatory properties through upregulation of heme oxygenase-1 via enhancement of porphyrin, indicating that it may be beneficial for the treatment of inflammatory conditions. This study systematically examines 5-ALA for use in inflammatory bowel disease (IBD). Firstly, the ex vivo colonic stability and permeability of 5-ALA was assessed using human and mouse fluid and tissue. Secondly, the in vivo efficacy of 5-ALA, in the presence of sodium ferrous citrate, was investigated via the oral and intracolonic route in an acute DSS colitis mouse model of IBD. Results showed that 5-ALA was stable in mouse and human colon fluid, as well as in colon tissue. 5-ALA showed more tissue restricted pharmacokinetics when exposed to human colonic tissue. In vivo dosing demonstrated significantly improved colonic inflammation, increased local heme oxygenase-1 levels, and decreased concentrations of proinflammatory cytokines TNF-α, IL-6, and IL-1β in both plasma and colonic tissue. These effects were superior to that measured concurrently with established anti-inflammatory treatments, ciclosporin and 5-aminosalicylic acid (mesalazine). As such, 5-ALA represents a promising addition to the IBD armamentarium, with potential for targeted colonic delivery. MDPI 2021-05-20 /pmc/articles/PMC8160866/ /pubmed/34065300 http://dx.doi.org/10.3390/biomedicines9050578 Text en © 2021 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 Yadav, Vipul Mai, Yang McCoubrey, Laura E. Wada, Yasufumi Tomioka, Motoyasu Kawata, Satofumi Charde, Shrikant Basit, Abdul W. 5-Aminolevulinic Acid as a Novel Therapeutic for Inflammatory Bowel Disease |
title | 5-Aminolevulinic Acid as a Novel Therapeutic for Inflammatory Bowel Disease |
title_full | 5-Aminolevulinic Acid as a Novel Therapeutic for Inflammatory Bowel Disease |
title_fullStr | 5-Aminolevulinic Acid as a Novel Therapeutic for Inflammatory Bowel Disease |
title_full_unstemmed | 5-Aminolevulinic Acid as a Novel Therapeutic for Inflammatory Bowel Disease |
title_short | 5-Aminolevulinic Acid as a Novel Therapeutic for Inflammatory Bowel Disease |
title_sort | 5-aminolevulinic acid as a novel therapeutic for inflammatory bowel disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160866/ https://www.ncbi.nlm.nih.gov/pubmed/34065300 http://dx.doi.org/10.3390/biomedicines9050578 |
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