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

Citation

Shastri, S and Shinde, T and Sohal, SS and Gueven, N and Eri, R, Idebenone Protects against Acute Murine Colitis via Antioxidant and Anti-Inflammatory Mechanisms, International Journal of Molecular Sciences, 21, (2) pp. 1-21. ISSN 1422-0067 (2020) [Refereed Article]


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

DOI: doi:10.3390/ijms21020484

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 Details

Item Type:Refereed Article
Keywords:idebenone, cytokines, inflammatory bowel disease, lipid peroxidation, superoxide dismutase, tight junction proteins and ulcerative colitis
Research Division:Medical and Health Sciences
Research Group:Pharmacology and Pharmaceutical Sciences
Research Field:Pharmaceutical Sciences
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Digestive System Disorders
UTAS Author:Shastri, S (Mrs Sonia Shastri)
UTAS Author:Shinde, T (Ms Tanvi Shinde)
UTAS Author:Sohal, SS (Dr Sukhwinder Sohal)
UTAS Author:Gueven, N (Dr Nuri Guven)
UTAS Author:Eri, R (Associate Professor Raj Eri)
ID Code:137231
Year Published:2020
Deposited By:Pharmacy
Deposited On:2020-02-05
Last Modified:2020-07-27
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