137231 - Idebenone Protects against Acute Murine Colitis.pdf (4.26 MB)
Idebenone Protects against Acute Murine Colitis via Antioxidant and Anti-Inflammatory Mechanisms
journal contribution
posted on 2023-05-20, 10:34 authored by Shastri, S, Shinde, TS, Sukhwinder SohalSukhwinder Sohal, Nuri GuvenNuri Guven, Rajaraman EriOxidative 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.
History
Publication title
International Journal of Molecular SciencesVolume
21Pagination
1-21ISSN
1422-0067Department/School
School of Health SciencesPublisher
Molecular Diversity Preservation InternationalPlace of publication
Matthaeusstrasse 11, Basel, Switzerland, Ch-4057Rights statement
Copyright 2020 The Authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/Repository Status
- Open