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.