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Idebenone Protects against Acute Murine Colitis via Antioxidant and Anti-Inflammatory Mechanisms

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Shastri, S, Shinde, TS ORCID: 0000-0002-8551-5841, Sohal, SS ORCID: 0000-0001-9627-6498, Gueven, N ORCID: 0000-0003-3782-767X and Eri, R ORCID: 0000-0003-1688-8043 2020 , 'Idebenone Protects against Acute Murine Colitis via Antioxidant and Anti-Inflammatory Mechanisms' , International Journal of Molecular Sciences, vol. 21, no. 2 , pp. 1-21 , doi: 10.3390/ijms21020484.

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Abstract

Oxidative stress is a key player of the inflammatory cascade responsible for the initiation of ulcerative colitis (UC). Although the short chain quinone idebenone is considered a potent antioxidant and a mitochondrial electron donor, emerging evidence suggests that idebenone also displays anti-inflammatory activity. This study evaluated the impact of idebenone in the widely used dextran sodium sulphate (DSS)-induced mouse model of acute colitis. Acute colitis was induced in C57BL/6J mice via continuous exposure to 2.5% DSS over 7 days. Idebenone was co-administered orally at a dose of 200 mg/kg body weight. Idebenone significantly prevented body weight loss and improved the disease activity index (DAI), colon length, and histopathological score. Consistent with its reported antioxidant function, idebenone significantly reduced the colonic levels of malondialdehyde (MDA) and nitric oxide (NO), and increased the expression of the redox factor NAD(P)H (nicotinamide adenine dinucleotide phosphate) dehydrogenase quinone-1 (NQO-1) in DSS-exposed mice. Immunohistochemistry revealed a significantly increased expression of tight junction proteins, which protect and maintain paracellular intestinal permeability. In support of an anti-inflammatory activity, idebenone significantly attenuated the elevated levels of pro-inflammatory cytokines in colon tissue. These results suggest that idebenone could represent a promising therapeutic strategy to interfere with disease pathology in UC by simultaneously inducing antioxidative and anti-inflammatory pathways.

Item Type: Article
Authors/Creators:Shastri, S and Shinde, TS and Sohal, SS and Gueven, N and Eri, R
Keywords: idebenone, cytokines, inflammatory bowel disease, lipid peroxidation, superoxide dismutase, tight junction proteins and ulcerative colitis
Journal or Publication Title: International Journal of Molecular Sciences
Publisher: Molecular Diversity Preservation International
ISSN: 1422-0067
DOI / ID Number: 10.3390/ijms21020484
Copyright Information:

Copyright 2020 The Authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/

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