V Yadav
5-Aminolevulinic Acid as a Novel Therapeutic for Inflammatory Bowel Disease
Yadav, V; Mai, Y; McCoubrey, LE; Wada, Y; Tomioka, M; Kawata, S; Charde, S; Basit, AW
Authors
Y Mai
LE McCoubrey
Y Wada
M Tomioka
S Kawata
S Charde
AW Basit
Abstract
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-alpha, IL-6, and IL-1 beta 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.
Citation
Yadav, V., Mai, Y., McCoubrey, L., Wada, Y., Tomioka, M., Kawata, S., …Basit, A. (2021). 5-Aminolevulinic Acid as a Novel Therapeutic for Inflammatory Bowel Disease. Biomedicines, 9(5), https://doi.org/10.3390/biomedicines9050578
Journal Article Type | Article |
---|---|
Acceptance Date | May 15, 2021 |
Publication Date | 2021 |
Deposit Date | Dec 21, 2021 |
Publicly Available Date | Dec 21, 2021 |
Publisher | MDPI |
Peer Reviewed | Peer Reviewed |
Volume | 9 |
Issue | 5 |
DOI | https://doi.org/10.3390/biomedicines9050578 |
Keywords | ulcerative colitis; Crohn's disease; inflammation; 5 amino levulinic acid; colonic drug delivery; anti-inflammatory; large intestine; drug stability; microbiota metabolism; microbiome; HEME OXYGENASE-1; FLUORESCENCE; RESECTION; EFFICACY; DELIVERY; SODIUM; |
Public URL | https://rvc-repository.worktribe.com/output/1553477 |
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