The effect of Losartan in the skeletal muscle morphology of Golden Retriever Muscular Dystrophy: a promising drug for the dystrophic muscle regeneration? / O Efeito do Losartan na morfologia do músculo esquelético do modelo Golden Retriever Muscular Dystrophy: uma droga promissora para a regeneração da musculatura distrófica?

AUTOR(ES)

Marina Brito Silva

DATA DE PUBLICAÇÃO

2009

RESUMO

Duchenne Muscular Dystophy (DMD) has the substitution of the muscle by connective tissue as its most relevant characteristic. Once fibrotic proliferation is a major obstacle to the efficacy of therapies for muscular dystrophies, early interventions to prevent it will probably be necessary as part of an effective treatment. A significant correlation between fibrosis and the expression of TGF-beta 1, a multifunctional cytokine, in Duchenne muscular dystrophies has been reported, emphasizing the role of this cytokine in the development of muscle fibrosis, and suggesting it as target for fibrotic therapies. In this study we evaluated the effect of Losartan over the development of the connective tissue on the skeletal musculature of the canine model GRMD. One dystrophic dog was previously used in the pilot study to estipulate the dosage and any side effects caused by Losartan. Five adults dystrophics dogs, two male and two female and one control animal were used in the experiment. A dose of 50mg of Losartan was orally given once a day. The clinical and laboratorial exams did not show any adverse effect through the experimental period, therefore Losartan utilization showed to be a safe therapy. Muscle biopsy fragments have been removed before starting Losartan (T0) and after (Tf) were used for histology and TGF-beta1 imunohistochemistry to compare this two times. The evaluations range of motion and limb circumference measures within imunohistochemistry and colagen quantification results helped to infer about Losartan effect in the dystrophic muscle fibrose. Range of motion and limb circumference values did not show statistical difference. Although the percentage of connective tissue deposition area in the animals in Tf was statistically lower than T0. The decrease of TGF-beta1 signalization showed in imunohistochemistry pictures within the decrease of connective tissue deposition, after Losartan, suggest an inhibitory effect of this medication through this cytokine in the studied GRMD muscle.

ASSUNTO(S)

golden retriever (grmd) losartan golden retriever (grmd) losartan muscle dystrophy distrofia muscular tgf-beta tgf-beta

Documentos Relacionados

• Influência da fisioterapia na função motora e histopatologia da fibra muscular esquelética no modelo Golden Retriever Muscular Dystrophy (GRMD)
• Golden Retriever Muscular Dystrophy (GRMD) como modelo morfofuncional da reparação tecidual na Distrofia Muscular de Duchenne
• Efeito do exercício aquático na regeneração do músculo esquelético após criolesão.
• Alterações do tubo digestório de cães da raça Golden Retriever afetados pela distrofia muscular
• Matrix metalloproteinase-9 inhibition ameliorates pathogenesis and improves skeletal muscle regeneration in muscular dystrophy