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Short-chain naphthoquinone protects against both acute and spontaneous chronic murine colitis by alleviating inflammatory responses

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posted on 2023-05-21, 01:47 authored by Shastri, S, Shinde, TS, Krystel WoolleyKrystel Woolley, Jason SmithJason Smith, Nuri GuvenNuri Guven, Rajaraman Eri
Ulcerative colitis (UC) is characterised by chronic, relapsing, idiopathic, and multifactorial colon inflammation. Recent evidence suggests that mitochondrial dysfunction plays a critical role in the onset and recurrence of this disease. Previous reports highlighted the potential of short-chain quinones (SCQs) for the treatment of mitochondrial dysfunction due to their reversible redox characteristics. We hypothesised that a recently described potent mitoprotective SCQ (UTA77) could ameliorate UC symptoms and pathology. In a dextran sodium sulphate- (DSS-) induced acute colitis model in C57BL/6J mice, UTA77 substantially improved DSS-induced body weight loss, disease activity index (DAI), colon length, and histopathology. UTA77 administration also significantly increased the expression of tight junction (TJ) proteins occludin and zona-occludin 1 (ZO-1), which preserved intestinal barrier integrity. Similar responses were observed in the spontaneous Winnie model of chronic colitis, where UTA77 significantly improved DAI, colon length, and histopathology. Furthermore, UTA77 potently suppressed elevated levels of proinflammatory cytokines and chemokines in colonic explants of both DSS-treated and Winnie mice. These results strongly suggest that UTA77 or its derivatives could be a promising novel therapeutic approach for the treatment of human UC.

History

Publication title

Frontiers in Pharmacology

Volume

12

Pagination

1-16

ISSN

1663-9812

Department/School

School of Health Sciences

Publisher

Frontiers Research Foundation

Place of publication

Switzerland

Rights statement

Copyright © 2021 Shastri, Shinde, Woolley, Smith, Gueven and Eri. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) License (https://creativecommons.org/licenses/by/4.0/).

Repository Status

  • Open

Socio-economic Objectives

Expanding knowledge in the biomedical and clinical sciences

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