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Idebenone Protects against Acute Murine Colitis via Antioxidant and Anti-Inflammatory Mechanisms
Citation
Shastri, S and Shinde, TS 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 Statement
Copyright 2020 The Authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/
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: | Biomedical and Clinical Sciences |
| Research Group: | Pharmacology and pharmaceutical sciences |
| Research Field: | Pharmaceutical sciences |
| Objective Division: | Health |
| Objective Group: | Clinical health |
| Objective Field: | Clinical health not elsewhere classified |
| UTAS Author: | Shastri, S (Mrs Sonia Shastri) |
| UTAS Author: | Shinde, TS (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 |
| Web of Science® Times Cited: | 23 |
| Deposited By: | Pharmacy |
| Deposited On: | 2020-02-05 |
| Last Modified: | 2020-07-27 |
| Downloads: | 15 View Download Statistics |
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