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Tytuł:
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Deferasirox alleviates DSS-induced ulcerative colitis in mice by inhibiting ferroptosis and improving intestinal microbiota.
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Autorzy:
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Wu Y; Department of Pathogen Biology and Immunology, Faculty of Basic Medical Science, Kunming Medical University, Kunming, China; Department of Anesthesiology, The First Affiliated Hospital of Kunming Medical University, Kunming, China.
Ran L; Department of Pathogen Biology and Immunology, Faculty of Basic Medical Science, Kunming Medical University, Kunming, China.
Yang Y; Department of Anesthesiology, The Affiliated Hospital of Yunnan University, Kunming, China.
Gao X; Department of Pathogen Biology and Immunology, Faculty of Basic Medical Science, Kunming Medical University, Kunming, China; Department of Anesthesiology, The First Affiliated Hospital of Kunming Medical University, Kunming, China.
Peng M; Department of Pathogen Biology and Immunology, Faculty of Basic Medical Science, Kunming Medical University, Kunming, China.
Liu S; Department of Pathogen Biology and Immunology, Faculty of Basic Medical Science, Kunming Medical University, Kunming, China.
Sun L; Department of Pathogen Biology and Immunology, Faculty of Basic Medical Science, Kunming Medical University, Kunming, China.
Wan J; Department of Vascular Surgery, The Affiliated Hospital of Yunnan University, Kunming, China.
Wang Y; Department of Pathogen Biology and Immunology, Faculty of Basic Medical Science, Kunming Medical University, Kunming, China.
Yang K; Department of Anesthesiology, The First Affiliated Hospital of Kunming Medical University, Kunming, China. Electronic address: .
Yin M; School of Medicine, Yunnan University, Kunming, China. Electronic address: .
Chunyu W; Department of Pathogen Biology and Immunology, Faculty of Basic Medical Science, Kunming Medical University, Kunming, China. Electronic address: .
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Źródło:
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Life sciences [Life Sci] 2023 Feb 01; Vol. 314, pp. 121312. Date of Electronic Publication: 2022 Dec 21.
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Typ publikacji:
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Journal Article
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Język:
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English
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Imprint Name(s):
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Publication: <2008->: Amsterdam : Elsevier
Original Publication: Oxford; Elmsford, N. Y. [etc.] Pergamon Press.
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MeSH Terms:
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Colitis, Ulcerative*/chemically induced
Colitis, Ulcerative*/drug therapy
Colitis, Ulcerative*/pathology
Gastrointestinal Microbiome*
Ferroptosis*
Colitis*/pathology
Mice ; Animals ; Deferasirox/metabolism ; RNA, Ribosomal, 16S/metabolism ; Colon/metabolism ; Sodium Chloride ; Sodium Chloride, Dietary/adverse effects ; Iron/metabolism ; Dextran Sulfate/pharmacology ; Mice, Inbred C57BL ; Disease Models, Animal
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Contributed Indexing:
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Keywords: Deferasirox; Ferroptosis; Intestinal microbiota; SCFAs; Ulcerative colitis
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Substance Nomenclature:
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V8G4MOF2V9 (Deferasirox)
0 (RNA, Ribosomal, 16S)
451W47IQ8X (Sodium Chloride)
0 (Sodium Chloride, Dietary)
E1UOL152H7 (Iron)
9042-14-2 (Dextran Sulfate)
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Entry Date(s):
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Date Created: 20221223 Date Completed: 20230120 Latest Revision: 20230120
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Update Code:
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20240105
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DOI:
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10.1016/j.lfs.2022.121312
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PMID:
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36563842
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Aims: Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) caused by multiple factors. Studies have shown that epithelial cell damage was associated with ferroptosis in UC. Therefore, our research focused on the effects and mechanism of iron chelator deferasirox in UC.
Main Methods: The UC model was induced by 2.5 % dextran sulfate sodium salt (DSS) and administered with deferasirox (10 mg/kg) for 7 days. Histological pathologies, inflammatory response, ferrous iron contents, oxidative stress and ferroptosis regulators were determined. Intestinal microbiota alteration and short-chain fatty acids (SCFAs) production were analyzed through 16S rRNA gene sequencing and targeted metabolomics.
Key Findings: Deferasirox significantly relieved the DSS-induced UC in mice, as evidenced by weight loss, survival rate, colon length shortening disease activity index (DAI) score and histology score. Deferasirox treatment reduced the level of pro inflammatory cytokines (IL-1β, IL-6, TNF-α and INF-γ). Ferroptosis was induced in mice with UC, as evidenced by ferrous iron accumulation, increased ROS production, SOD and GSH depletion, decreased the expression of GPX-4 and FTH, accompanied by increased expression of TF. Deferasirox treatment strongly reversed the alterations caused by ferroptotic characteristics in DSS-induced mice. Moreover, deferasirox treatment reshaped the composition of intestinal microbiota. The results revealed the genera of norank_f__Muribaculaceae, Lachnospiraceae_NK4A136_group, Prevotellaceae_UCG-001, Odoribacter and Blautia were increased distinctly, while Escherichia-Shigella and Streptococcus were significantly decreased by deferasirox treatment. Targeted metabolomics analysis indicated the SCFAs production enhanced in deferasirox-treated mice.
Significance: Our results suggested that deferasirox could treat DSS-induced UC in mice by inhibiting ferroptosis and improving intestinal microbiota.
Competing Interests: Declaration of competing interest The authors declared that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2022. Published by Elsevier Inc.)
