Examining potential drug therapies for muscular dystrophy utilising the dy/dy mouse: I. Clenbuterol.
As a potent promoter of muscle growth, clenbuterol has been proposed as a treatment for muscle wasting diseases. Thus, the effects of clenbuterol on dystrophic skeletal muscle was examined. Male dystrophic (dy/dy) mice aged 4-5 weeks were treated with clenbuterol for 3 weeks, and the isometric contractile, fatigue and histochemical properties of the slow-twitch soleus and fast-twitch plantaris muscles measured. Muscles of dystrophic animals produced lower forces, contracted more slowly and exhibited greater fatigue resistance than age-matched normal animals. Dystrophic soleus muscles also had higher proportions of type I fibres than normal mice. Clenbuterol significantly reduced the natural death rate of dystrophic mice, as 3 of 11 untreated animals died prior to completion of the 3-week experimental period, whereas none of the 9 clenbuterol-treated animals died. Clenbuterol treatment significantly increased the relative mass (P<0.001) and relative tetanic force production (P<0.01) of the soleus of dystrophic animals, most likely due to increases in protein accretion and improved regeneration. The plantaris of clenbuterol-treated dystrophic animals also exhibited higher mass (P<0.05) and higher absolute forces than untreated mice. The results from this study show that clenbuterol could be a valuable adjunct to treatments of muscle wasting diseases such as muscular dystrophy.
Hayes
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Department of Physiology, The University of Melbourne, Parkville, Victoria, Australia. AlanHayes@vut.edu.au
Williams
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D000284:Administration, Oral; D000818:Animals; D002976:Clenbuterol / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D006321:Heart / Q000187:drug effects; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009119:Muscle Contraction / Q000187:drug effects; D018763:Muscle Fatigue / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects / Q000473:pathology; D009137:Muscular Dystrophy, Animal / Q000235:genetics / Q000401:mortality / Q000503:physiopathology*; D009929:Organ Size / Q000187:drug effects
D002976:Clenbuterol