{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T22:43:09Z","timestamp":1780440189308,"version":"3.54.1"},"reference-count":31,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T00:00:00Z","timestamp":1718150400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001602","name":"Science Foundation Ireland","doi-asserted-by":"publisher","award":["FFP\/19\/6628 INSPIRE DMD"],"award-info":[{"award-number":["FFP\/19\/6628 INSPIRE DMD"]}],"id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Duchenne muscular dystrophy (DMD) is characterised by respiratory muscle injury, inflammation, fibrosis and weakness, ultimately culminating in respiratory failure. The dystrophin\u2010deficient mouse model of DMD (<jats:italic>mdx<\/jats:italic>) shows evidence of respiratory muscle remodelling and dysfunction contributing to impaired respiratory system performance. The antioxidant <jats:italic>N<\/jats:italic>\u2010acetylcysteine (NAC) has been shown to exert anti\u2010inflammatory and anti\u2010fibrotic effects leading to improved respiratory muscle performance in a range of animal models of muscle dysfunction, including <jats:italic>mdx<\/jats:italic> mice, following short\u2010term administration (2\u00a0weeks). We sought to build on previous work by exploring the effects of chronic NAC administration (3\u00a0months) on respiratory system performance in <jats:italic>mdx<\/jats:italic> mice. One\u2010month\u2010old male <jats:italic>mdx<\/jats:italic> mice were randomised to receive normal drinking water (<jats:italic>n<\/jats:italic>\u00a0=\u00a030) or 1% NAC in the drinking water (<jats:italic>n<\/jats:italic>\u00a0=\u00a030) for 3\u00a0months. At 4\u00a0months of age, we assessed breathing in conscious mice by plethysmography followed by <jats:italic>ex vivo<\/jats:italic> assessment of diaphragm force\u2010generating capacity. Additionally, diaphragm histology was performed. In separate studies, in anaesthetised mice, respiratory electromyogram (EMG) activity and inspiratory pressure across a range of behaviours were determined, including assessment of peak inspiratory pressure\u2010generating capacity. NAC treatment did not affect force\u2010generating capacity of the <jats:italic>mdx<\/jats:italic> diaphragm. Collagen content and immune cell infiltration were unchanged in <jats:italic>mdx<\/jats:italic> + NAC compared with <jats:italic>mdx<\/jats:italic> diaphragms. Additionally, there was no significant effect of NAC on breathing, ventilatory responsiveness, inspiratory EMG activity or inspiratory pressure across the range of behaviours from basal conditions to peak system performance. We conclude that chronic NAC treatment has no apparent beneficial effects on respiratory system performance in the <jats:italic>mdx<\/jats:italic> mouse model of DMD suggesting limited potential of NAC treatment alone for human DMD.<\/jats:p>","DOI":"10.1113\/ep091862","type":"journal-article","created":{"date-parts":[[2024,6,13]],"date-time":"2024-06-13T05:44:01Z","timestamp":1718257441000},"page":"1370-1384","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Chronic <i>N<\/i>\u2010acetyl cysteine treatment does not improve respiratory system performance in the <i>mdx<\/i> mouse model of Duchenne muscular dystrophy"],"prefix":"10.1113","volume":"109","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3728-1673","authenticated-orcid":false,"given":"Michael N.","family":"Maxwell","sequence":"first","affiliation":[{"name":"Department of Physiology University College Cork  Cork Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1460-7167","authenticated-orcid":false,"given":"Anthony L.","family":"Marullo","sequence":"additional","affiliation":[{"name":"Department of Physiology University College Cork  Cork Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Valverde\u2010P\u00e9rez","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular y Fisiolog\u00eda, Facultad de Medicina Universidad de Valladolid  Valladolid Spain"},{"name":"Unidad de Excelencia Instituto Biomedicina y Gen\u00e9tica Molecular (IBGM) Universidad de Valladolid\u2010CSIC  Valladolid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aoife D.","family":"Slyne","sequence":"additional","affiliation":[{"name":"Department of Physiology University College Cork  Cork Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9618-1990","authenticated-orcid":false,"given":"Ben T.","family":"Murphy","sequence":"additional","affiliation":[{"name":"Department of Physiology University College Cork  Cork Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8832-1153","authenticated-orcid":false,"given":"Ken D.","family":"O'Halloran","sequence":"additional","affiliation":[{"name":"Department of Physiology University College Cork  Cork Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,6,12]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.20586"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox6040101"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP276954"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox8120581"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP277443"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP274792"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12051124"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004240100561"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/6842568"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/thx.52.5.472"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pmrj.2009.04.010"},{"key":"e_1_2_9_13_1","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1002\/cphy.c140048","volume-title":"Comprehensive physiology","author":"Gao Q. 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