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Open Access 01-12-2013 | Research article

Mitochondria-targeted antioxidant MitoQ ameliorates experimental mouse colitis by suppressing NLRP3 inflammasome-mediated inflammatory cytokines

Authors: Amarjargal Dashdorj, Jyothi KR, Sangbin Lim, Ara Jo, Minh Nam Nguyen, Joohun Ha, Kyung-Sik Yoon, Hyo Jong Kim, Jae-Hoon Park, Michael P Murphy, Sung Soo Kim

Published in: BMC Medicine | Issue 1/2013

Abstract

Background

MitoQ is a mitochondria-targeted derivative of the antioxidant ubiquinone, with antioxidant and anti-apoptotic functions. Reactive oxygen species are involved in many inflammatory diseases including inflammatory bowel disease. In this study, we assessed the therapeutic effects of MitoQ in a mouse model of experimental colitis and investigated the possible mechanisms underlying its effects on intestinal inflammation.

Methods

Reactive oxygen species levels and mitochondrial function were measured in blood mononuclear cells of patients with inflammatory bowel disease. The effects of MitoQ were evaluated in a dextran sulfate sodium-induced colitis mouse model. Clinical and pathological markers of disease severity and oxidative injury, and levels of inflammatory cytokines in mouse colonic tissue were measured. The effect of MitoQ on inflammatory cytokines released in the human macrophage-like cell line THP-1 was also analyzed.

Results

Cellular and mitochondrial reactive oxygen species levels in mononuclear cells were significantly higher in patients with inflammatory bowel disease (P <0.003, cellular reactive oxygen species; P <0.001, mitochondrial reactive oxygen species). MitoQ significantly ameliorated colitis in the dextran sulfate sodium-induced mouse model in vivo, reduced the increased oxidative stress response (malondialdehyde and 3-nitrotyrosine formation), and suppressed mitochondrial and histopathological injury by decreasing levels of inflammatory cytokines IL-1 beta and IL-18 (P <0.001 and P <0.01 respectively). By decreasing mitochondrial reactive oxygen species, MitoQ also suppressed activation of the NLRP3 inflammasome that was responsible for maturation of IL-1 beta and IL-18. In vitro studies demonstrated that MitoQ decreases IL-1 beta and IL-18 production in human THP-1 cells.

Conclusion

Taken together, our results suggest that MitoQ may have potential as a novel therapeutic agent for the treatment of acute phases of inflammatory bowel disease.

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The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1741-7015/11/178/prepub

Title: Mitochondria-targeted antioxidant MitoQ ameliorates experimental mouse colitis by suppressing NLRP3 inflammasome-mediated inflammatory cytokines
Authors: Amarjargal Dashdorj
Jyothi KR
Sangbin Lim
Ara Jo
Minh Nam Nguyen
Joohun Ha
Kyung-Sik Yoon
Hyo Jong Kim
Jae-Hoon Park
Michael P Murphy
Sung Soo Kim
Publication date: 01-12-2013
Publisher: BioMed Central
Published in: BMC Medicine / Issue 1/2013
Electronic ISSN: 1741-7015
DOI: https://doi.org/10.1186/1741-7015-11-178

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Mitochondria-targeted antioxidant MitoQ ameliorates experimental mouse colitis by suppressing NLRP3 inflammasome-mediated inflammatory cytokines

Abstract

Background

Methods

Results

Conclusion

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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