Abstract
We sought to determine the effectiveness of poloxamer 188 (P188) in protecting dystrophin-deficient, mdx skeletal muscle fiber membrane against exercise-induced breaches. mdx mice were treated with either P188 or placebo via intraperitoneal injections and run on a treadmill for 60-90 min. Membrane breakdown was quantified in cross-sections of rectus femoris muscle pretreated with Evans blue dye (in vivo). The mean % dye-penetrated muscle in the P188 and placebo groups was not significantly different in each of three trials. These results contrast with a recent report of P188 being highly effective in protecting the stretch- and dobutamine-stressed mdx heart muscle. The most likely explanations for the disparity are: (1) the exercise stress we used was beyond the protective range of P188, (2) P188 delivery and serum concentration were sub-optimal, or (3) the mdx skeletal myopathy and cardiomyopathy have fundamentally different responses to treatment.
MeSH terms
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Animals
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Cardiomyopathies / drug therapy
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Cardiomyopathies / metabolism
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Cardiomyopathies / physiopathology
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Cell Membrane Permeability / drug effects*
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Cell Membrane Permeability / physiology
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Coloring Agents
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Disease Models, Animal
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Dose-Response Relationship, Drug
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Drug Administration Routes
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Exercise Tolerance / drug effects
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Exercise Tolerance / physiology
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Female
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Injections, Intraperitoneal
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Inbred mdx
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Muscle Contraction / drug effects
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Muscle Contraction / physiology
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Muscle Fibers, Skeletal / drug effects*
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Muscle Fibers, Skeletal / metabolism
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Muscle Fibers, Skeletal / pathology
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Muscle, Skeletal / drug effects*
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Muscle, Skeletal / metabolism
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Muscle, Skeletal / physiopathology
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Muscular Dystrophy, Duchenne / drug therapy*
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Muscular Dystrophy, Duchenne / metabolism
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Muscular Dystrophy, Duchenne / physiopathology
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Physical Conditioning, Animal / physiology
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Poloxamer / pharmacology*
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Poloxamer / therapeutic use
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Sarcolemma / drug effects*
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Sarcolemma / metabolism
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Surface-Active Agents / pharmacology
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Surface-Active Agents / therapeutic use
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Treatment Failure
Substances
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Coloring Agents
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Surface-Active Agents
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Poloxamer