Idebenone Protects against Acute Murine Colitis via Antioxidant and Anti-Inflammatory Mechanisms
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-infla...
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doaj-9383bc6f3582441496700d48099ef96e2020-11-25T01:10:11ZengMDPI AGInternational Journal of Molecular Sciences1422-00672020-01-0121248410.3390/ijms21020484ijms21020484Idebenone Protects against Acute Murine Colitis via Antioxidant and Anti-Inflammatory MechanismsSonia Shastri0Tanvi Shinde1Sukhwinder Singh Sohal2Nuri Gueven3Rajaraman Eri4Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, Tasmania 7250, AustraliaDepartment of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, Tasmania 7250, AustraliaDepartment of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, Tasmania 7250, AustraliaPharmacy, School of Medicine, College of Health and Medicine, University of Tasmania, Hobart, Tasmania 7005, AustraliaDepartment of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, Tasmania 7250, AustraliaOxidative 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.https://www.mdpi.com/1422-0067/21/2/484idebenonecytokinesinflammatory bowel diseaselipid peroxidationsuperoxide dismutasetight junction proteins and ulcerative colitis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sonia Shastri Tanvi Shinde Sukhwinder Singh Sohal Nuri Gueven Rajaraman Eri |
spellingShingle |
Sonia Shastri Tanvi Shinde Sukhwinder Singh Sohal Nuri Gueven Rajaraman Eri Idebenone Protects against Acute Murine Colitis via Antioxidant and Anti-Inflammatory Mechanisms International Journal of Molecular Sciences idebenone cytokines inflammatory bowel disease lipid peroxidation superoxide dismutase tight junction proteins and ulcerative colitis |
author_facet |
Sonia Shastri Tanvi Shinde Sukhwinder Singh Sohal Nuri Gueven Rajaraman Eri |
author_sort |
Sonia Shastri |
title |
Idebenone Protects against Acute Murine Colitis via Antioxidant and Anti-Inflammatory Mechanisms |
title_short |
Idebenone Protects against Acute Murine Colitis via Antioxidant and Anti-Inflammatory Mechanisms |
title_full |
Idebenone Protects against Acute Murine Colitis via Antioxidant and Anti-Inflammatory Mechanisms |
title_fullStr |
Idebenone Protects against Acute Murine Colitis via Antioxidant and Anti-Inflammatory Mechanisms |
title_full_unstemmed |
Idebenone Protects against Acute Murine Colitis via Antioxidant and Anti-Inflammatory Mechanisms |
title_sort |
idebenone protects against acute murine colitis via antioxidant and anti-inflammatory mechanisms |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2020-01-01 |
description |
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. |
topic |
idebenone cytokines inflammatory bowel disease lipid peroxidation superoxide dismutase tight junction proteins and ulcerative colitis |
url |
https://www.mdpi.com/1422-0067/21/2/484 |
work_keys_str_mv |
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