Antioxidants Reduce Muscular Dystrophy in the dy2J/dy2J Mouse Model of Laminin α2 Chain-Deficient Muscular Dystrophy
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animals
2.2. Human Tissues
2.3. Treatments
2.4. Stand Ups and Grip Strength
2.5. Tissue Collection
2.6. Histology and Immunohistochemistry
2.7. Morphometric Evaluation of Fibrosis by Fast Green and Sirius Red Staining
2.8. Colorimetric Evaluation of Fibrosis by Fast Green/Sirius Red Staining
2.9. Dihydroethidium Staining for ROS Detection
2.10. Real Time PCR Analysis
2.11. Statistical Analysis and Data Availability
3. Results
3.1. Significantly Increased ROS Levels in Skeletal Muscles of dy2J/dy2J Mice and LAMA2-CMD Patients
3.2. Muscle Force Loss is Prevented by NAC Treatment
3.3. Skeletal Muscle Histology is Preserved by Both NAC and Vitamin E Treatment
3.4. Fibrosis is Prevented in NAC Treated dy2J/dy2J Muscles
3.5. Inflammation and Increased ROS Levels are Prevented in Response to NAC and Vitamin E
3.6. Apoptosis is Prevented upon NAC Treatment
4. Discussion
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Individual | Muscle | Age at Biopsy | LAMA2 Mutation | Laminin α2- Deficiency | DHE Positive Area (%) |
---|---|---|---|---|---|
Patients | Quadriceps | 4 years | Unknown | Partial | 4.94 |
Unknown | 17 years | Unknown | Complete | 5.27 | |
Unknown | 22 days | Homo c.2208 + 2T>C | Complete | 10.55 | |
Radial forearm | 29 years | Homo c.2230C>T | Partial | 4.23 | |
Deltoid | 2 years | Unknown | Complete | 6.42 | |
Deltoid | 3.5 years | Unknown | Complete | 10.27 | |
Controls | Radial forearm | 33 years | - | - | 3.56 |
Quadriceps | 17 years | - | - | 3.10 | |
Vastus | 2 months | - | - | 2.34 | |
Unknown | 2.5 years | - | - | 1.88 |
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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 dy2J/dy2J Mouse Model of Laminin α2 Chain-Deficient Muscular Dystrophy. Antioxidants 2020, 9, 244. https://doi.org/10.3390/antiox9030244
M. Harandi V, Moreira Soares Oliveira B, Allamand V, Friberg A, Fontes-Oliveira CC, Durbeej M. Antioxidants Reduce Muscular Dystrophy in the dy2J/dy2J Mouse Model of Laminin α2 Chain-Deficient Muscular Dystrophy. Antioxidants. 2020; 9(3):244. https://doi.org/10.3390/antiox9030244
Chicago/Turabian StyleM. Harandi, Vahid, Bernardo Moreira Soares Oliveira, Valérie Allamand, Ariana Friberg, Cibely C. Fontes-Oliveira, and Madeleine Durbeej. 2020. "Antioxidants Reduce Muscular Dystrophy in the dy2J/dy2J Mouse Model of Laminin α2 Chain-Deficient Muscular Dystrophy" Antioxidants 9, no. 3: 244. https://doi.org/10.3390/antiox9030244