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| Author(s): |
Samara Camaçarí De Carvalho
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | Campinas, SP. |
| Institution: | Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia |
| Defense date: | 2016-07-29 |
| Examining board members: |
Maria Julia Marques;
Edmar Zanoteli;
Elen Haruka Miyabara;
Tânia Aparecida Marchiori de Oliveira Cardoso;
César Renato Sartori
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| Advisor: | Maria Julia Marques |
| Abstract | |
Duchenne muscular dystrophy (DMD) is the most severe dystrophinopathy and results from the lack of dystrophin in skeletal and cardiac muscles. The inflammatory response is exacerbated and contributes to the progression of the disease leading to fibrosis and difficulting muscle regeneration. M2 macrophages can activate myogenic cells and can promote fibrosis, in the long run. In the present study we investigated the effects of omega-3 on fibrosis, inflammation, regeneration and metabolites in the early (16 days of therapy) and later (5 months of therapy) stages of the disease. Mdx mice (14 days or 3 months of age) received 300mg/kg of omega-3 by gavage 3 times a week for 16 days or 5 months. Mdx and C57BL/10 (control) mice received mineral oil by gavage in the same volume and period. We verified that omega-3 improved muscular force, decreased myonecrosis (CK reduction in plasma) and improved regeneration (MyoD and area with regenerating fibers) in heart, diaphragm and quadriceps muscles. Omega-3 reduced the pro-inflammatory factors TNF-? and NF-?B after 16 days (in all dystrophic muscles) and after 5 months (only in mdx diaphragm) of treatment. In all muscles and in both treatment periods there was a predominance of M2 (shown by high levels of CD206, IL-10 and IL -13) over the M1 (indicated by reduced levels of INF-?, IL-6 and iNOS). The levels of TGF-?1 decreased in the short (diaphragm) and in the long (heart) term therapies. There was a significant increase in fibrosis area in all muscles studied after the 5-month therapy. The metabolites glutamate, glutamine, taurine, creatine, ascorbato and oxypurinol showed changes related to disease progression and omega-3 therapy interfered in most of these metabolites. Overall, the present study indicates that, despite the beneficial effects of omega-3 in muscle force, myonecrosis, inflammation, regeneration and metabolites, 5 months therapy with omega-3 needs caution and further studies of omega-3 effects on fibrosis pathways and metabolism are necessary (AU) | |
| FAPESP's process: | 12/15492-3 - Pharmacological therapy of the dystrophinopathies: fibrosis and muscular regeneration in mdx mice treated with omega-3 |
| Grantee: | Samara Camaçarí de Carvalho |
| Support Opportunities: | Scholarships in Brazil - Doctorate |