N-acetylcysteine decreases fibrosis and increases force-generating capacity of mdx diaphragm

Simple item page
dc.contributor.authorBurns, David P.
dc.contributor.authorDrummond, Sarah E.
dc.contributor.authorBolger, Dearbhla
dc.contributor.authorCoiscaud, Amélie
dc.contributor.authorMurphy, Kevin H.
dc.contributor.authorEdge, Deirdre
dc.contributor.authorO'Halloran, Ken D.
dc.contributor.funderTrinity College Dublinen
dc.contributor.funderUniversity College Corken
dc.contributor.funderThe Physiological Societyen
dc.date.accessioned2019-12-09T12:47:17Z
dc.date.available2019-12-09T12:47:17Z
dc.date.issued2019-11-24
dc.description.abstractRespiratory muscle weakness occurs due to dystrophin deficiency in Duchenne muscular dystrophy (DMD). The mdx mouse model of DMD shows evidence of impaired respiratory muscle performance with attendant inflammation and oxidative stress. We examined the effects of N-acetylcysteine (NAC) supplementation on respiratory system performance in mdx mice. Eight-week-old male wild type (n = 10) and mdx (n = 20) mice were studied; a subset of mdx (n = 10) received 1% NAC in the drinking water for 14 days. We assessed breathing, diaphragm, and external intercostal electromyogram (EMG) activities and inspiratory pressure during ventilatory and non-ventilatory behaviours. Diaphragm muscle structure and function, cytokine concentrations, glutathione status, and mRNA expression were determined. Diaphragm force-generating capacity was impaired in mdx compared with wild type. Diaphragm muscle remodelling was observed in mdx, characterized by increased muscle fibrosis, immune cell infiltration, and central myonucleation. NAC supplementation rescued mdx diaphragm function. Collagen content and immune cell infiltration were decreased in mdx + NAC compared with mdx diaphragms. The cytokines IL-1β, IL-6 and KC/GRO were increased in mdx plasma and diaphragm compared with wild type; NAC decreased systemic IL-1β and KC/GRO concentrations in mdx mice. We reveal that NAC treatment improved mdx diaphragm force-generating capacity associated with beneficial anti-inflammatory and anti-fibrotic effects. These data support the potential use of NAC as an adjunctive therapy in human dystrophinopathies.en
dc.description.sponsorshipTrinity College Dublin (Department of Physiology); University College Cork (Department of Physiology)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleid581en
dc.identifier.citationBurns, D. P., Drummond, S. E., Bolger, D., Coiscaud, A., Murphy, K. H., Edge, D. and O’Halloran, K. D. (2019) 'N-acetylcysteine Decreases Fibrosis and Increases Force-Generating Capacity of mdx Diaphragm', Antioxidants, 8(12), 581 (26pp). doi: 10.3390/antiox8120581en
dc.identifier.doi10.3390/antiox8120581en
dc.identifier.eissn2076-3921
dc.identifier.endpage26en
dc.identifier.issued12en
dc.identifier.journaltitleAntioxidantsen
dc.identifier.startpage1en
dc.identifier.urihttps://hdl.handle.net/10468/9366
dc.identifier.volume8en
dc.language.isoenen
dc.publisherMDPI AGen
dc.rights© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectAntioxidanten
dc.subjectN-acetylcysteineen
dc.subjectDMDen
dc.subjectMdxen
dc.subjectDisphragmen
dc.subjectIntercostalen
dc.subjectInterleuki-6en
dc.subjectInterleukin-1βen
dc.subjectFibrosisen
dc.titleN-acetylcysteine decreases fibrosis and increases force-generating capacity of mdx diaphragmen
dc.typeArticle (peer-reviewed)en
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
antioxidants-08-00581.pdf
Size:
953.57 KB
Format:
Adobe Portable Document Format
Description:
Published version
Download
License bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
license.txt
Size:
2.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Medicine - Journal Articles
Physiology - Journal Articles