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Abstract

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.

Item Type:	Article
Authors/Creators:	Shastri, S and Shinde, T and Woolley, KL and Smith, JA and Gueven, N and Eri, R
Keywords:	cytokines, endoplasmic reticulum stress, inflammatory bowel disease, naphthoquinones, tight junction proteins
Journal or Publication Title:	Frontiers in Pharmacology
Publisher:	Frontiers Research Foundation
ISSN:	1663-9812
DOI / ID Number:	10.3389/fphar.2021.709973
Copyright Information:	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/).
Related URLs:	UTAS Profile: Woolley, KL Google Scholar: Smith, JA UTAS Profile: Smith, JA Google Scholar: Gueven, N UTAS Profile: Gueven, N Google Scholar: Eri, R UTAS Profile: Eri, R
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