Effect of diacerein and vitamin E on dystrophic fibers of mdx mice

Author(s)

Rafael Dias Mâncio

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
• Defense date: 2017-06-09

Examining board members

Elaine Minatel; Adriana Fogagnolo Maurício; Cintia Yuri Matsumura; Rosana Macher Teodori; Stella Regina Zamuner

• Advisor: Elaine Minatel

Abstract

Duchenne muscular dystrophy (DMD) is considered the most common and devastating of human muscular dystrophies. Chronic inflammation and oxidative stress are striking features of disease. Diacerein is an anthraquinone used in the osteoarthritis treatment, which exhibits anti-inflammatory and antioxidant properties and the Vitamin E presents an important role as a potent antioxidant and in preserving the integrity of the cell membrane. The aim of the present study was evaluated the effects of Diacerein and Vitamin E against myonecrosis, oxidative stress and inflammatory response in the diaphragm, sternomastoid and tibialis anterior muscles of mdx mice. In this study, C57BL/10 and mdx mice were used. The mdx mice were randomly divided into 5 groups: mdx (treated with saline); mdxP (treated with Prednisone ¿ 5mg/kg; positive control); mdxD (treated with Diacerein ¿ 20mg/kg); mdxVE (treated with Vitamin E ¿ 40mg/kg) and mdxVED (treated with Vitamin E and Diacerein). The C57BL/10 mice received no treatment and were used as a control group. All animals were submitted to force measurement analysis. Blood samples were used for the determination of creatine kinase (CK) and for the quantification of IL-1? and IL-6 levels. The diaphragm (DIA), sternomastoid (STN) and tibialis anterior (TA) muscles were removed and submitted to histological techniques (HE, IgG, F4/80, DHE and lipofuscin), Western blotting (TNF-?, NF-?B, 4-HNE, SOD2, Catalase, GR) and for the determination of GSH activity. The results showed that mdx mice treated with Diacerein, Vitamin E and/or association of these two drugs presented a reduction in strength loss, muscle damage, exacerbated inflammatory response and oxidative damage. Compared with Prednisone treatment, the results demonstrated that treatment with Diacerein and Vitamin E improved the dystrophic phenotype of the muscles analyzed, similar to that observed with glucocorticoid treatment. Taken together, the results demonstrate the beneficial effects of treatment with Diacerein and Vitamin E, administered alone or in combination, in the process of muscle regeneration, inflammatory response and oxidative stress in the DIA, STN and TA muscles of mdx mice (AU)

• FAPESP's process: 14/01970-6 - Effect of Diacerein and vitamin E on dystrophic muscle fibers of mdx mice
• Grantee: Rafael Dias Mâncio
• Support Opportunities: Scholarships in Brazil - Doctorate