Effect of Sodium Butyrate on the dystrophic phenotype in mdx mice

• Grant number: 25/02372-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: May 01, 2025
• End date: April 30, 2026
• Field of knowledge: Biological Sciences - Morphology - Anatomy
• Principal Investigator: Renato Ferretti
• Grantee: Maria Eduarda Oliveira Matheus
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Despite the absence of the dystrophin protein causing Duchenne muscular dystrophy (DMD), secondary events such as increased calcium (Ca2+) levels, inflammation, and reactive oxygen and nitrogen species (RONS) are correlated with the worsening of the Duchenne muscular dystrophy (DMD) phenotype. These events trigger the reduction and/or functional loss of ventilation. Increased intracellular Ca2+ levels with reduced expression of Ca2+ regulatory proteins, increased inflammatory mediators such as TNF-alpha (TNF-a), and RONS appear to be related to myonecrosis in mdx mice, a model of DMD. DMD, so far, has no cure and therapies have been advocated that can reduce side effects and improve muscle function. Sodium butyrate (NaB), a short-chain fatty acid byproduct of carbohydrate digestion, rescued muscle strength, reduced inflammation, and reduced oxidative stress in mice. NaB inhibits pro-inflammatory cytokines IFN-gamma, TNF-a, IL-1beta, IL-6, and IL-8, while IL-10 and TGF-beta are upregulated. NaB increased the expression of genes involved in the active intestinal absorption of Ca2+. However, little is known about the effect of NaB on the management of Ca2+ levels, inflammation, and RONS in improving the function and phenotype of dystrophic fibers. The aim of this project is to evaluate the effects of NaB treatment on the levels of Ca2+ regulatory proteins, inflammation, and RONS in the muscles of dystrophic mdx mice. We will use mdx mice treated daily with NaB (5mg/kg; via gavage, for 14 days). It is expected that NaB can reduce free Ca2+ with greater homeostasis of regulatory proteins, improve the inflammatory process, reduce oxidative stress, and improve respiratory function of dystrophic mdx mice.