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Article Publish Status: FREE
Abstract Title:

N-acetylcysteine Decreases Fibrosis and Increases Force-Generating Capacity ofDiaphragm.

Abstract Source:

Antioxidants (Basel). 2019 Nov 24 ;8(12). Epub 2019 Nov 24. PMID: 31771272

Abstract Author(s):

David P Burns, Sarah E Drummond, Dearbhla Bolger, Amélie Coiscaud, Kevin H Murphy, Deirdre Edge, Ken D O'Halloran

Article Affiliation:

David P Burns

Abstract:

Respiratory muscle weakness occurs due to dystrophin deficiency in Duchenne muscular dystrophy (DMD). Themouse 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 inmice. Eight-week-old male wild type (= 10) and(= 20) mice were studied; a subset of(= 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 incompared with wild type. Diaphragm muscle remodelling was observed in, characterized by increased muscle fibrosis, immune cell infiltration, and central myonucleation. NAC supplementation rescueddiaphragm function. Collagen content and immune cell infiltration were decreased in+ NAC compared withdiaphragms. The cytokines IL-1β, IL-6 and KC/GRO were increased inplasma and diaphragm compared with wild type; NAC decreased systemic IL-1β and KC/GRO concentrations inmice. We reveal that NAC treatment improveddiaphragm 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.

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