PREDNISONE CAN PROTECT AGAINST EXERCISE-INDUCED MUSCLE DAMAGE

Ln an experimental animal exercise model we tested whether daily admin istration of prednisone prevents the development of mechanically induc ed muscle fibre damage. Six-week-old rats were treated with different doses of prednisone ranging from 1 to 50 mg/kg body weight per day or with placebo, for 8 days. On day 6 of treatment the rats were forced t o run for 2 h on a level treadmill. Two days after exercise morphologi cal damage in the soleus muscles was quantified using light microscopy and a semi-automatic image analysis system. Creatine kinase (CK) acti vity was measured before exercise (day 5) and directly after exercise (day 6). The expression of dystrophin in a placebo group and in a grou p that received 5 mg prednisone/kg body weight per day with and withou t performing exercise was studied with Western blotting. The effect of prednisone on fibre type distribution was determined with an antibody against fast myosin and the effect of prednisone on the proliferative activity of muscle satellite cells was studied using bromodeoxyuridin e (BrdU) immunohistochemistry. Exercise-induced muscle fibre damage va ried in a dose-dependent way. In the placebo group the mean (SEM) dama ged muscle fibre area was 4% (1%). The groups that received low doses of prednisone, 1 or 2.5 mg/kg per day, showed a similar level of muscl e damage. However, with 5 mg prednisone/kg per day the amount of muscl e fibre damage [mean (SEM)] was significantly reduced to 1.4% (0.5%) ( P less than or equal to 0.05, Student's t-test). High doses of prednis one had no protective effect. Directly after exercise the CK activity was increased two-fold, except in the group that received 50 mg predni sone/kg body weight per day. No changes in the amount of dystrophin we re found after densitometric analysis of the Western blots. Prednisone did not affect the fibre distribution or the labelling index of satel lite cells. We conclude that prednisone, given in an appropriate dose, protects muscle fibres against the development of mechanically induce d damage, possibly by stabilizing the muscle fibre membranes, This act ion may explain the beneficial effect of prednisone observed in Duchen ne muscular dystrophy patients.