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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...

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Autores principales: Yadav, Vipul, Mai, Yang, McCoubrey, Laura E., Wada, Yasufumi, Tomioka, Motoyasu, Kawata, Satofumi, Charde, Shrikant, Basit, Abdul W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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.
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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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