Antioxidants Reduce Muscular Dystrophy in the dy2J/dy2J Mouse Model of Laminin α2 Chain-Deficient Muscular Dystrophy

M. Harandi, Vahid; Moreira Soares Oliveira, Bernardo; Allamand, Valérie; Friberg, Ariana; Fontes-Oliveira, Cibely C.; Durbeej, Madeleine

doi:10.3390/antiox9030244

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Antioxidants Reduce Muscular Dystrophy in the dy^2J/dy^2J Mouse Model of Laminin α2 Chain-Deficient Muscular Dystrophy

Vahid M. Harandi

^1,*

Bernardo Moreira Soares Oliveira

^1,2

Valérie Allamand

^1,3,

Ariana Friberg

¹,

Cibely C. Fontes-Oliveira

and

Madeleine Durbeej

Unit of Muscle Biology, Department of Experimental Medical Science, Lund University, 221 84 Lund, Sweden

Functional Genomics & Metabolism Unit, Department of Biochemistry & Molecular Biology, University of Southern Denmark, 5230 Odense, Denmark

Centre de Recherche en Myologie, Sorbonne Université, Inserm, UMRS974, 75013 Paris, France

Author to whom correspondence should be addressed.

Antioxidants 2020, 9(3), 244; https://doi.org/10.3390/antiox9030244

Received: 24 January 2020 / Revised: 28 February 2020 / Accepted: 17 March 2020 / Published: 18 March 2020

(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)

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Abstract

Congenital muscular dystrophy with laminin α2 chain-deficiency (LAMA2-CMD) is a severe neuromuscular disorder without a cure. Using transcriptome and proteome profiling as well as functional assays, we previously demonstrated significant metabolic impairment in skeletal muscle from LAMA2-CMD patients and mouse models. Reactive oxygen species (ROS) increase when oxygen homeostasis is not maintained and, here, we investigate whether oxidative stress indeed is involved in the pathogenesis of LAMA2-CMD. We also analyze the effects of two antioxidant molecules, N-acetyl-L-cysteine (NAC) and vitamin E, on disease progression in the dy^2J/dy^2J mouse model of LAMA2-CMD. We demonstrate increased ROS levels in LAMA2-CMD mouse and patient skeletal muscle. Furthermore, NAC treatment (150 mg/kg IP for 6 days/week for 3 weeks) led to muscle force loss prevention, reduced central nucleation and decreased the occurrence of apoptosis, inflammation, fibrosis and oxidative stress in LAMA2-CMD muscle. In addition, vitamin E (40 mg/kg oral gavage for 6 days/week for 2 weeks) improved morphological features and reduced inflammation and ROS levels in dy^2J/dy^2J skeletal muscle. We suggest that NAC and to some extent vitamin E might be potential future supportive treatments for LAMA2-CMD as they improve numerous pathological hallmarks of LAMA2-CMD. View Full-Text

Keywords: laminin; reactive oxygen species; congenital muscular dystrophy; therapy

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M. Harandi, V.; Moreira Soares Oliveira, B.; Allamand, V.; Friberg, A.; Fontes-Oliveira, C.C.; Durbeej, M. Antioxidants Reduce Muscular Dystrophy in the dy^2J/dy^2J Mouse Model of Laminin α2 Chain-Deficient Muscular Dystrophy. Antioxidants 2020, 9, 244. https://doi.org/10.3390/antiox9030244

AMA Style

M. Harandi V, Moreira Soares Oliveira B, Allamand V, Friberg A, Fontes-Oliveira CC, Durbeej M. Antioxidants Reduce Muscular Dystrophy in the dy^2J/dy^2J Mouse Model of Laminin α2 Chain-Deficient Muscular Dystrophy. Antioxidants. 2020; 9(3):244. https://doi.org/10.3390/antiox9030244

Chicago/Turabian Style

M. Harandi, Vahid, Bernardo Moreira Soares Oliveira, Valérie Allamand, Ariana Friberg, Cibely C. Fontes-Oliveira, and Madeleine Durbeej. 2020. "Antioxidants Reduce Muscular Dystrophy in the dy^2J/dy^2J Mouse Model of Laminin α2 Chain-Deficient Muscular Dystrophy" Antioxidants 9, no. 3: 244. https://doi.org/10.3390/antiox9030244

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Antioxidants Reduce Muscular Dystrophy in the dy^2J/dy^2J Mouse Model of Laminin α2 Chain-Deficient Muscular Dystrophy

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