Effect of Diacerein and vitamin E on dystrophic muscle fibers of mdx mice

• Grant number: 14/01970-6
• Support type: Scholarships in Brazil - Doctorate
• Effective date (Start): October 01, 2014
• Effective date (End): February 28, 2017
• Field of knowledge: Biological Sciences - Morphology - Anatomy
• Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal researcher: Elaine Minatel
• Grantee: Rafael Dias Mâncio
• Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Intense inflammatory process and oxidative stress are factors that contribute to the physiopathogenesis of dystrophic muscle fibers. Among the mechanisms involved in the inflammatory response in Duchenne muscular dystrophy (DMD) and mdx mice (experimental model of DMD), highlights the signaling pathway of NF-ºB factor whose the primary action via is the activation of cytokines pro-inflammatory such as tumor necrosis factor alpha (TNF-±) and interleukin IL-1². In addition, the reactive oxygen species (ROS) have also been related to the activation of NF-ºB factor in the dystrophic muscle fibers. Given the above, in this project we hypothesized that the treatment with anti-inflammatory DIACEREIN associated with the antioxidant Vitamin E may have potential therapeutic effect on dystrophic muscle fibers of mdx mice. Studies have shown that diacerein inhibit the synthesis and activity of cytokines pro-inflammatory such as TNF-±, IL-6 and IL-1², while the Vitamin E prevents lipid peroxidation of membrane efficiently. To verify the hypothesis, C57BL/10 (control group) and mdx mice, 14 days of postnatal life will be used. The mdx mice and C57BL/10 will be divided into 4 experimental groups: saline treated, treated with diacerein, treated with Vitamin E and/or with the association with diacerein and Vitamin E. All animals will be subjected to strength measurement analysis before and after the treatment. Blood samples will be used for the creatine kinase (CK) and TNF-±, IL-1² and IL-6 quantification. The sternomastoid (STN) , diaphragm (DIA) and anterior tibialis (TA) muscles will be removed and submitted to morphological techniques (quantification of regenerated and degeneration fibers; inflammation area and lipofuscin), Western Blotting (TNF-±, NF-ºB, IL-1², IL -6 and 4- HNE), determination of enzymatic activity of GPx , GR and SOD and glutathione oxidized and reduced by liquid chromatography ultra efficiency. The results will be analyzed statistically. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

HERMES, TULIO DE ALMEIDA; MANCIO, RAFAEL DIAS; MACEDO, ALINE BARBOSA; MIZOBUTI, DANIELA SAYURI; DA ROCHA, GUILHERME LUIZ; ALVES CAGNON, VALERIA HELENA; MINATEL, ELAINE. Tempol treatment shows phenotype improvement in mdx mice. PLoS One, v. 14, n. 4 APR 22 2019. Web of Science Citations: 2.

MANCIO, RAFAEL DIAS; HERMES, TULIO DE ALMEIDA; MACEDO, ALINE BARBOSA; MIZOBUTI, DANIELA SAYURI; VALDUGA, AMANDA HARDUIM; RUPCIC, IAN FELLER; MINATEL, ELAINE. Vitamin E treatment decreases muscle injury in mdx mice. NUTRITION, v. 43-44, p. 39-46, NOV-DEC 2017. Web of Science Citations: 3.

MANCIO, RAFAEL DIAS; HERMES, TULIO DE ALMEIDA; MACEDO, ALINE BARBOSA; MIZOBUTI, DANIELA SAYURI; RUPCIC, IAN FELLER; MINATEL, ELAINE. Dystrophic phenotype improvement in the diaphragm muscle of mdx mice by diacerhein. PLoS One, v. 12, n. 8 AUG 7 2017. Web of Science Citations: 3.

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

MÂNCIO, Rafael Dias. Effect of diacerein and vitamin E on dystrophic fibers of mdx mice. 2017. Doctoral Thesis - Universidade Estadual de Campinas, Instituto de Biologia.