Treatment With Full-Spectrum Cannabidiol Oil Improved the Pathological Findings of Dystrophic Mutant Mice
Laís Leite Ferreira
Department of Anatomy, Federal University of Alfenas (UNIFAL-MG), Alfenas, Brazil
Contribution: Methodology, Investigation, Validation, Formal analysis, Data curation, Writing - original draft
Search for more papers by this authorFabricio Souza Gomes
Department of Anatomy, Federal University of Alfenas (UNIFAL-MG), Alfenas, Brazil
Contribution: Methodology, Investigation, Formal analysis
Search for more papers by this authorBeatriz Godinho Nascimento
Department of Anatomy, Federal University of Alfenas (UNIFAL-MG), Alfenas, Brazil
Contribution: Methodology, Formal analysis
Search for more papers by this authorWagner Corsini
Department of Anatomy, Federal University of Alfenas (UNIFAL-MG), Alfenas, Brazil
Contribution: Methodology
Search for more papers by this authorLuis Felipe Cunha dos Reis
Department of Structural Biology, Federal University of Alfenas (UNIFAL-MG), Alfenas, Brazil
Contribution: Methodology, Formal analysis
Search for more papers by this authorJoão Marcos Oliveira-Silva
Natural Sciences Institute, Federal University of Alfenas (UNIFAL-MG), Alfenas, Brazil
Contribution: Investigation, Methodology, Formal analysis, Data curation
Search for more papers by this authorJosie Resende Torres da Silva
Motor Sciences Institute, Federal University of Alfenas (UNIFAL-MG), Alfenas, Brazil
Contribution: Writing - review & editing, Resources
Search for more papers by this authorMarcelo Lourenço da Silva
Motor Sciences Institute, Federal University of Alfenas (UNIFAL-MG), Alfenas, Brazil
Contribution: Writing - review & editing, Resources
Search for more papers by this authorAngel Maurício Castro Gamero
Natural Sciences Institute, Federal University of Alfenas (UNIFAL-MG), Alfenas, Brazil
Contribution: Funding acquisition, Writing - review & editing, Visualization, Resources, Supervision
Search for more papers by this authorCorresponding Author
Túlio de Almeida Hermes
Department of Anatomy, Federal University of Alfenas (UNIFAL-MG), Alfenas, Brazil
Correspondence:
Túlio de Almeida Hermes ([email protected]; [email protected])
Contribution: Conceptualization, Project administration, Resources, Funding acquisition, Writing - original draft, Validation, Data curation, Supervision
Search for more papers by this authorLaís Leite Ferreira
Department of Anatomy, Federal University of Alfenas (UNIFAL-MG), Alfenas, Brazil
Contribution: Methodology, Investigation, Validation, Formal analysis, Data curation, Writing - original draft
Search for more papers by this authorFabricio Souza Gomes
Department of Anatomy, Federal University of Alfenas (UNIFAL-MG), Alfenas, Brazil
Contribution: Methodology, Investigation, Formal analysis
Search for more papers by this authorBeatriz Godinho Nascimento
Department of Anatomy, Federal University of Alfenas (UNIFAL-MG), Alfenas, Brazil
Contribution: Methodology, Formal analysis
Search for more papers by this authorWagner Corsini
Department of Anatomy, Federal University of Alfenas (UNIFAL-MG), Alfenas, Brazil
Contribution: Methodology
Search for more papers by this authorLuis Felipe Cunha dos Reis
Department of Structural Biology, Federal University of Alfenas (UNIFAL-MG), Alfenas, Brazil
Contribution: Methodology, Formal analysis
Search for more papers by this authorJoão Marcos Oliveira-Silva
Natural Sciences Institute, Federal University of Alfenas (UNIFAL-MG), Alfenas, Brazil
Contribution: Investigation, Methodology, Formal analysis, Data curation
Search for more papers by this authorJosie Resende Torres da Silva
Motor Sciences Institute, Federal University of Alfenas (UNIFAL-MG), Alfenas, Brazil
Contribution: Writing - review & editing, Resources
Search for more papers by this authorMarcelo Lourenço da Silva
Motor Sciences Institute, Federal University of Alfenas (UNIFAL-MG), Alfenas, Brazil
Contribution: Writing - review & editing, Resources
Search for more papers by this authorAngel Maurício Castro Gamero
Natural Sciences Institute, Federal University of Alfenas (UNIFAL-MG), Alfenas, Brazil
Contribution: Funding acquisition, Writing - review & editing, Visualization, Resources, Supervision
Search for more papers by this authorCorresponding Author
Túlio de Almeida Hermes
Department of Anatomy, Federal University of Alfenas (UNIFAL-MG), Alfenas, Brazil
Correspondence:
Túlio de Almeida Hermes ([email protected]; [email protected])
Contribution: Conceptualization, Project administration, Resources, Funding acquisition, Writing - original draft, Validation, Data curation, Supervision
Search for more papers by this authorFunding: This work was supported by National Council for Scientific and Technological Development (CNPq) grant 402493/2021-4, by Coordination of Superior Level Staff Improvement (CAPES) Financing Code 001; doctoral scholarship: 88887.799640/2022-00;88881.708989/2022-01, and by Research Support Foundation of the State of Minas Gerais (FAPEMIG) APQ-02291-18; Doctoral Scholarship, #12988.
ABSTRACT
Introduction/Aims
Duchenne muscular dystrophy (DMD) is caused by pathogenic variants in the DMD gene, making muscle fibers susceptible to contraction-induced membrane damage. Given the potential beneficial action of cannabidiol (CBD), we evaluated the in vitro effect of full-spectrum CBD oil on the viability of dystrophic muscle fibers and the in vivo effect on myopathy of the mdx mouse, a DMD model.
Methods
In vitro, dystrophic cells from the mdx mouse were treated with full-spectrum CBD oil and assessed with cell viability and cytotoxic analyses. In vivo, fourteen-day-old mdx mice received 10 mg/kg/day of the full-spectrum CBD oil for 14 days. We analyzed creatine kinase (CK) levels, liver damage markers, and histopathology of the diaphragm (DIA) and quadriceps (QUA [myonecrotic fibers with positive IgG staining, regenerated fibers/central nuclei, the minimum Feret's diameter, the fibrosis area, the inflammatory area, the presence of macrophages, and NF-kappa B content]).
Results
In vitro treatment with full-spectrum CBD oil showed a dose-dependent cytotoxic effect; however, in vivo 10 mg/kg treatment was safe and effectively improved DMD histopathological assessment parameters in DIA and QUA: reduction of central nuclei: 1.7% ± 2.0% versus 22.4% ± 5.3% and 11.1% ± 10.7% versus 32.3% ± 4.6%; reduction of IgG+ myofibers: 0.6% ± 0.7% versus 8.4% ± 1.6% and 0.9% ± 0.3% versus 7.5% ± 1.0%; increase in myofiber size: 85.2 ± 3.2 versus 64.3 ± 4.0 μm and 106.5 ± 8.6 versus 81.2 ± 4.8 μm; decrease in inflammatory area: 6.2% ± 2.7% versus 15.1% ± 2.6% and 5.3 ± 4.1 versus 17.3% ± 2.8%; reduced macrophage area: 0.05% ± 0.1% versus 10.8% ± 4.3% and 1.0% ± 0.7% versus 10.3% ± 4.9%; NF-κB levels: 0.6% ± 0.1% versus 1.7% ± 0.2% and 1.7% ± 0.1% versus 5.2% ± 2.1%; and fibrosis: 5.6% ± 1.8% versus 12.0% ± 3.7% and 1.3% ± 0.5% versus 4.7% ± 1.5%. It also reduced serum CK.
Discussion
Full-spectrum CBD oil may represent a promising new approach to treating DMD, but its potential toxicity must be considered.
Graphical Abstract
In vitro and in vivo full-spectrum CBD effects in the mdx mice model. Created with BioRender.com.
Conflicts of Interest
The authors declare no conflicts of interest.
Open Research
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Supporting Information
| Filename | Description |
|---|---|
| mus28337-sup-0001-supinfo.docxWord 2007 document , 14.9 KB |
Data S1: Supporting Information. |
| mus28337-sup-0002-FigureS1.tifTIFF image, 10.4 MB |
Figure S1: Western blotting analysis of GAPDH content in the cell cultures. Bands corresponding to proteins (top row) and Ponceau S staining used as a loading control (bottom row) are shown from Ctrl, Vehicle, Ethanol 25%, CBD 18.75 μM (minimum dose) and 300 μM (maximum dose) groups. |
| mus28337-sup-0003-TableS1.docxWord 2007 document , 13.8 KB |
Table S1: List of cannabinoids and terpenes in the full-spectrum cannabidiol oil. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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