corticosterone-acetate and Muscular-Dystrophy--Animal

Primary cultures of muscle from normal (line 412) and dystrophic (line 413) chick embryos were exposed to corticosterone-21-acetate (C-21-A) or sodium ibuprofen (Motrin) for 28 d after myotube formation. Ibuprofen (0.5 to 500 micrograms/ml) or C-21-A (0.4 to 40 micrograms/ml)-treated cultures were fixed and assessed semiquantitatively using phase microscopy. On this basis, ibuprofen (50 micrograms/ml) and C-21-A (40 micrograms/ml) seemed to be effective in maintaining both normal and dystrophic muscle cultures. Using ibuprofen and C-21-A at these concentrations, experiments were repeated and analyzed quantitatively. Ibuprofen maintained culture viability (up to 68% more myotubes than untreated controls) but had no significant effect on the number of striated cells. C-21-A effectively maintained culture viability (up to 73% increase) and strongly promoted the formation of striated cells in these cultures (up to a sixfold increase). Both normal and dystrophic cultures were affected similarly by these agents, but the dystrophic cultures showed more consistent if not more extensive improvements in the parameters examined here. Thus, it seems that ibuprofen and C-21-A may affect both normal and dystrophic muscle directly to maintain survival and even promote differentiation.

Topics: Animals; Cell Differentiation; Cell Survival; Cells, Cultured; Chick Embryo; Corticosterone; Ibuprofen; Muscles; Muscular Dystrophy, Animal; Time Factors

In a previous series of 22-day evaluations of 31 compounds, only corticosterone-21-acetate (C-21-A) increased righting ability of genetically dystrophic chickens to a greater extent than the standard of comparison, methysergide maleate. In the present study, C-21-A was subjected to longer-term trials of up to 48 days, and additional signs of the myopathy were examined. The highest doses of C-21-A increased righting ability for the duration of the trials, decreased the typically elevated plasma levels of creatine kinase (CK) activity by more than 80%, and improved morphology of the dystrophic pectoralis major muscle at the light microscopic level. The major adverse effect of C-21-A, reduction of body weight, was consistently observed at the relatively high doses needed to increase righting ability. That alone, however, could not account for increased righting ability, and plasma CK activity was decreased even at doses that did not reduce body weight. The results show that C-21-A is the most effective compound yet tested in this system and, perhaps more significantly, provides the first evidence that it is possible to identify compounds that improve muscle morphology in a hereditary myopathy using a short-term, step-wise system.

Topics: Animals; Chickens; Corticosterone; Creatine Kinase; Drug Evaluation, Preclinical; Male; Muscles; Muscular Dystrophy, Animal; Poultry Diseases

Topics: Animals; Body Weight; Chickens; Corticosterone; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Fatigue; Female; Male; Methysergide; Muscular Dystrophy, Animal; Triamterene