Effects of citral on dystrophic diaphragm in mdx mice.

• Grant number: 25/18155-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: November 01, 2025
• End date: October 31, 2026
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Cintia Yuri Matsumura
• Grantee: Guilherme Cenci Mescolatti
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Duchenne muscular dystrophy (DMD) is a lethal pediatric disorder with no cure, exhibiting an epidemiological prevalence of approximately 2.8 cases per 100,000 births. DMD progressively compromises skeletal striated muscle function, leading to loss of ambulation and impairment of vital activities. Current treatment with glucocorticoids provides palliative care by delaying symptoms and disease progression; however, chronic administration is associated with multiple adverse effects. In this context, research into novel adjuvant or alternative therapies has been pursued. Our study will investigate the pharmacological effects of citral administration in the dystrophic muscle of mdx mice, an experimental model for DMD. Citral exhibits anti-inflammatory and antioxidant effects in the gastrointestinal tract, along with neuroprotective, renoprotective, and antinociceptive properties, without reported side effects. However, no studies have yet examined the effects of citral on dystrophic muscle. The diaphragm is among the most severely affected organs in DMD, contributing to progressive respiratory failure in humans as the disease advances. This phenotypic manifestation is similarly observed in the murine model. Therefore, we will analyze the diaphragm and blood of these animals using histological, biochemical, and molecular techniques to assess potential modulations in disease phenotype following citral treatment. The methodology includes morphometric analysis of transverse-sectional areas of normal and dystrophic muscle fibers, as well as regions exhibiting inflammatory and regenerative features. In addition to tissue analysis, molecular biology experiments will be conducted, including quantification of inflammation-related proteins (TNF-¿ and F4/80) via Western blotting, along with biochemical assays measuring plasma creatine kinase levels. The findings will expand current knowledge on the effects of citral and may contribute to innovative therapeutic strategies for DMD, either as a standalone treatment or in combination with corticosteroids.