Trilobatin contributes to the improvement of myopathy in a mouse model of Duchenne muscular dystrophy.
Tulio de Almeida HermesPaula FratiniBeatriz Godinho NascimentoLaís Leite FerreiraGiuliana PetriFernando Luiz Affonso FonsecaAlzira Alves de Siqueira CarvalhoDavid FederPublished in: International journal of experimental pathology (2024)
Duchenne muscular dystrophy (DMD) occurs due to genetic mutations that lead to a deficiency in dystrophin production and consequent progressive degeneration of skeletal muscle fibres, through oxidative stress and an exacerbated inflammatory process. The flavonoid trilobatin (TLB) demonstrates antioxidant and anti-inflammatory potential. Its high safety profile and effective action make it a potent therapy for the process of dystrophic muscle myonecrosis. Thus, we sought to investigate the action of TLB on damage in a DMD model, the mdx mouse. Eight-week-old male animals were treated with 160 mg/kg/day of trilobatin for 8 weeks. Control animals were treated with saline. Following treatment, muscle strength, serum creatine kinase (CK) levels, histopathology (necrotic myofibres, regenerated fibres/central nuclei, Feret's diameter and inflammatory area) and the levels of catalase and NF-κB (western blotting) of the quadriceps (QUA), diaphragm (DIA) and tibialis anterior (TA) muscles were measured. TLB was able to significantly increase muscle strength and reduce serum CK levels in dystrophic animals. The QUA of mdx mice showed a reduction in catalase and the number of fibres with a centralized nucleus after treatment with TLB. In the DIA of dystrophic animals, TLB reduced the necrotic myofibres, inflammatory area and NF-κB and increased the number of regenerated fibres and the total fibre diameter. In TA, TLB increased the number of regenerated fibres and reduced catalase levels in these animals. It is concluded that in the mdx experimental model, treatment with TLB was beneficial in the treatment of DMD.
Keyphrases
- duchenne muscular dystrophy
- oxidative stress
- muscular dystrophy
- skeletal muscle
- anti inflammatory
- mouse model
- signaling pathway
- dna damage
- gene expression
- combination therapy
- multiple sclerosis
- adipose tissue
- clinical trial
- randomized controlled trial
- south africa
- risk assessment
- genome wide
- study protocol
- dna methylation
- inflammatory response
- climate change
- newly diagnosed
- intensive care unit
- high fat diet induced
- tyrosine kinase
- human health
- heat shock