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

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dc.contributor.author Burns, David P.
dc.contributor.author Drummond, Sarah E.
dc.contributor.author Bolger, Dearbhla
dc.contributor.author Coiscaud, Amélie
dc.contributor.author Murphy, Kevin H.
dc.contributor.author Edge, Deirdre
dc.contributor.author O'Halloran, Ken D.
dc.date.accessioned 2019-12-09T12:47:17Z
dc.date.available 2019-12-09T12:47:17Z
dc.date.issued 2019-11-24
dc.identifier.citation Burns, 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/antiox8120581 en
dc.identifier.volume 8 en
dc.identifier.issued 12 en
dc.identifier.startpage 1 en
dc.identifier.endpage 26 en
dc.identifier.uri http://hdl.handle.net/10468/9366
dc.identifier.doi 10.3390/antiox8120581 en
dc.description.abstract Respiratory 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.sponsorship Trinity College Dublin (Department of Physiology); University College Cork (Department of Physiology) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher MDPI AG en
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.uri http://creativecommons.org/licenses/by/4.0/ en
dc.subject Antioxidant en
dc.subject N-acetylcysteine en
dc.subject DMD en
dc.subject Mdx en
dc.subject Disphragm en
dc.subject Intercostal en
dc.subject Interleuki-6 en
dc.subject Interleukin-1β en
dc.subject Fibrosis en
dc.title N-acetylcysteine decreases fibrosis and increases force-generating capacity of mdx diaphragm en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother David Burns, School of Medicine, Department of Physiology, University College Cork, Cork, Ireland. +353-21-490-3000 Email:david.burns@ucc.ie en
dc.internal.availability Full text available en
dc.description.version Published Version en
dc.contributor.funder Trinity College Dublin en
dc.contributor.funder University College Cork en
dc.contributor.funder The Physiological Society en
dc.description.status Peer reviewed en
dc.identifier.journaltitle Antioxidants en
dc.internal.IRISemailaddress david.burns@ucc.ie en
dc.internal.IRISemailaddress k.ohalloran@ucc.ie en
dc.identifier.articleid 581 en
dc.identifier.eissn 2076-3921


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© 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/). Except where otherwise noted, this item's license is described as © 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/).
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