Clenbuterol reduces degeneration of exercised or aged dystrophic (mdx) muscle.
Evidence of dystrophic muscle degeneration in the hind limb muscles of young (20-week-old) treadmill-exercised or aged (87-week-old) sedentary mdx mice was greatly reduced by treatment with clenbuterol, a beta(2)-adrenoceptor agonist. Daily treadmill exercise for 10 weeks increased the size of regions within the mdx plantaris but not the soleus or gastrocnemius muscles, in which necrotic muscle fibers or the absence of fibers was observed. Clenbuterol reduced the size of these abnormal regions from 21% of total muscle cross-sectional area to levels (4%) found in sedentary mdx mice. In addition, the muscles obtained from aged clenbuterol-treated mdx or wild-type mice did not display the extensive fibrosis or fiber loss observed in untreated mdx mice. These observations are consistent with a mechanism of dystrophic muscle degeneration caused by work load-induced injury that is cumulative with aging and is opposed by beta(2)-adrenoceptor activation. Optimization of beta(2)-agonist treatment of muscular dystrophy in mdx mice may lead to a useful therapeutic modality for human forms of the disease.
Zeman
R J
RJ
Department of Cell Biology and Anatomy, New York Medical College, Valhalla, New York 10595, USA. Zeman@nymc.edu
Peng
H
H
Danon
M J
MJ
Etlinger
J D
JD
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000375:Aging / Q000502:physiology*; D000818:Animals; D002976:Clenbuterol / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000254:growth & development / Q000473:pathology / Q000503:physiopathology; D009137:Muscular Dystrophy, Animal / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control; D010805:Physical Conditioning, Animal / Q000502:physiology*; D005082:Physical Exertion / Q000187:drug effects / Q000502:physiology*
D000318:Adrenergic beta-Agonists; D002976:Clenbuterol