ABSTRACT
Duchenne muscular dystrophy (DMD) is a severe X-linked recessive disorder characterized by the progressive loss of muscular strength. Mdx mutant mice show a marked deficiency in dystrophin, which was related to muscle membrane stability. The aim of this study was to verify the possible protective anti-inflammatory effect of citrus oil on mdx muscle fibers. Thus, adult male and female mdx mice (014/06-CEEA) were divided into control and citrus-treated. After 60 days of treatment, one ml of blood was collected for creatine kinase (CK) test. Diaphragm, sternomastoideus, anterior tibial and gastrocnemius muscles were removed and processed according to histological routine methods. The observed alterations indicate a direct effect of citrus. Recent studies have improved the diagnosis of muscular diseases but with no definitions of efficient treatments. Intervention with several therapies is important to many patients presenting muscular dystrophy, which enables them to live longer and be more active, while there is no development of gene therapies.
La distrofia muscular de Duchenne (DMD) es una enfermedad grave ligada al cromosoma X, trastorno recesivo que se caracteriza por la pérdida progresiva de fuerza muscular. Mdx ratones mutantes muestran una marcada deficiencia en la distrofina, que está relacionada con la estabilidad de la membrana muscular. El objetivo de este estudio fue comprobar el posible efecto protector, antiinflamatorio del aceite de cítricos en las fibras musculares mdx. Los ratones mdx adultos machos y hembras (014/06-CEEA) se dividieron en control y cítricos tratados. Después de 60 días de tratamiento, un ml de sangre fue recogida para cuantificar la creatina quinasa (CK) de prueba. Fueron retirados y procesados los músculos diafragma, esternomastoideo, tibial anterior y gastrocnemio de acuerdo con los métodos de rutina histológica. Las alteraciones observadas indican un efecto directo de los cítricos. Estudios recientes han mejorado el diagnóstico de enfermedades musculares, pero sin definiciones de tratamientos eficaces. Intervención con varias terapias es importante para muchos pacientes que presentan distrofia muscular, lo que les permite vivir más y ser más activos, mientras no exista desarrollo de terapias génicas.
Subject(s)
Animals , Rats , Oils, Volatile/administration & dosage , Citrus/chemistry , Muscular Dystrophy, Duchenne/drug therapy , Muscle, Skeletal , Regeneration , Anti-Inflammatory Agents , Creatine Kinase/analysis , Muscle Fibers, Skeletal , Mice, Inbred mdxABSTRACT
OBJECTIVE: To investigate the effect of steroid administration on the apoptosis and heat shock protein 70 (HSP70) expression after exercise in the animal model of Duchenne muscular dystrophy. METHOD: We measured Bcl-2, BAX and HSP70 expression by western blotting. 20 control and 20 mdx mice were divided into free-living (n=10) and exercise (n=10) groups. Free-living and exercise groups were further divided into steroid-treated and sham-treated groups to evaluate the effect of steroid administration. RESULTS: Apoptosis was most prominent in the sham-treated exercise group, while apoptosis was significantly reduced in the steroid-treated exercise group. HSP70 expression was maximized in sham-treated exercise group, whereas steroid administration inhibited HSP70 expression after exercise in muscular dystrophy animal model. Exercise loading was found to cause severe apoptosis but steroid administration alleviated apoptotic damage in mdx mice. CONCLUSION: HSP70 expression was suppressed in the steroid-treated exercise group, which suggests steroid might have major preventive effect in exercise-induced apoptosis of muscular dystrophy animal model.
Subject(s)
Animals , Mice , Apoptosis , Blotting, Western , Heat-Shock Proteins , Hot Temperature , HSP70 Heat-Shock Proteins , Mice, Inbred mdx , Models, Animal , Muscular DystrophiesABSTRACT
OBJECTIVE: To investigate the effect of exercise and steroid to the muscle of animal model of Duchenne muscular dystrophy. METHOD: We used 15 mdx and 15 control mice. To grade exercise loading, control and mdx mice were divided into free-living, exercise and immobilization groups. Free-living and exercise groups were further divided into steroid-treated and sham-treated groups to evaluate the effect of steroid administration. We measured the apoptotic changes using in situ DNA nick-end labling (TUNEL), DNA fragmentation assay and western blots for Bcl-2 and BAX. RESULT: With TUNEL method, the largest number of myonuclei became positive in sham-treated exercise group while apoptosis was significantly reduced in steroid-treated exercise group in mdx mice. Steroid-treated free-living group showed higher rate of apoptotic change than sham-treated free-living group. With western blots for Bcl-2 and BAX, the value of BAX/Bcl-2 ratio was highest in sham-treated exercise group and among free living mdx mice, it was higher in steroid-treated group than sham-treated one. CONCLUSION: Apoptosis can be minimized in free living condition while exercise loading or immobilization can cause apoptotic change in muscular dystrophy animal model. Steroid administration induces apoptosis in free living muscle and it alleviates apoptotic damage caused by exercise loading in mdx mice.
Subject(s)
Animals , Mice , Apoptosis , Blotting, Western , DNA , DNA Fragmentation , Immobilization , In Situ Nick-End Labeling , Mice, Inbred mdx , Models, Animal , Muscle, Skeletal , Muscular Dystrophies , Muscular Dystrophy, Duchenne , Social ConditionsABSTRACT
PURPOSE: To observe dystrophin formation and histological improvement in dystrophic muscle of mdx mouse after normal myoblast injection. MATERIALS AND METHODS: Cultured myoblasts from genetically normal rats were injected into the right quadriceps femoris of a 6-week-old mdx mouse (n=9). dPBS was injected into the left quadriceps femoris as a control. One, 2, and 3 months after injection, The control and experimental group were compared histologically and by dystrophin immunostaining. RESULTS: When compared with controls 3 months postoperatively, quadriceps femoris in the experimental group exhibited greater cross-sectional area and total fiber number, and the experimental animals contained more normal-appearing and less abnormalappearing fibers than the control group. Most of the fibers in the experimental group showed positive results in dystrophin immunostaining, whereas immunostaining of mdx muscle fibers in the control group was completely negative. CONCLUSION: This study shows that normal myoblast injection improved the muscle architecture histologically and produced dystrophin protein in dystrophic muscle.