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Poloxamer 188 failed to prevent exercise-induced membrane breakdown in mdx skeletal muscle fibers
Authors:Quinlan John G  Wong Brenda L  Niemeier Richard T  McCullough Alexandra S  Levin Linda  Emanuele Martin
Affiliation:

aDepartment of Neurology, The University of Cincinnati, 4010 Medical Science Building, 231 Albert Sabin Way, Cincinnati, OH 45267-0525, USA

bDepartments of Epidemiology and Statistics, The University of Cincinnati, Cincinnati, OH, USA

cCincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

dSynthRx Corporation, 150 Technology Parkway, Norcross, GA, USA

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.
Keywords:mdx mouse   Poloxamer 188   Sarcolemma   Dystrophin-deficient   Exercise
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