Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Vahid M. Harandi
* ORCID logo ,
Bernardo Moreira Soares Oliveira
,
Valérie Allamand
,
Ariana Friberg
,
Cibely C Fontes-Oliveira
ORCID logo ,
Madeleine Durbeej
Version 1 : Received: 24 January 2020 / Approved: 27 January 2020 / Online: 27 January 2020 (09:34:14 CET)

A peer-reviewed article of this Preprint also exists.

Harandi, V.M.; Oliveira, B.M.S.; Allamand, V.; Friberg, A.; Fontes-Oliveira, C.C.; Durbeej, M. Antioxidants Reduce Muscular Dystrophy in the dy2J/dy2J Mouse Model of Laminin α2 Chain-Deficient Muscular Dystrophy. Antioxidants 2020, 9, 244. Harandi, V.M.; Oliveira, B.M.S.; Allamand, V.; Friberg, A.; Fontes-Oliveira, C.C.; Durbeej, M. Antioxidants Reduce Muscular Dystrophy in the dy2J/dy2J Mouse Model of Laminin α2 Chain-Deficient Muscular Dystrophy. Antioxidants 2020, 9, 244.

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 analyse the effects of two antioxidant molecules, N-acetyl-L-cysteine (NAC) and vitamin E, on disease progression in the dy2J/dy2J 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 during 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 during 2 weeks) improved morphological features and reduced inflammation and ROS levels in dy2J/dy2J 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.

Keywords

laminin; reactive oxygen species; congenital muscular dystrophy; therapy

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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