Poloxamer 188 failed to prevent exercise-induced membrane breakdown in mdx skeletal muscle fibers.
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.
Quinlan
John G
JG
Department of Neurology, The University of Cincinnati, 4010 Medical Science Building, Cincinnati, OH 45267-0525, USA. john.quinlan@uc.edu
Wong
Brenda L
BL
Niemeier
Richard T
RT
McCullough
Alexandra S
AS
Levin
Linda
L
Emanuele
Martin
M
D000818:Animals; D009202:Cardiomyopathies / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D002463:Cell Membrane Permeability / Q000187:drug effects* / Q000502:physiology; D004396:Coloring Agents; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D017079:Exercise Tolerance / Q000187:drug effects / Q000502:physiology; D005260:Female; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D020388:Muscular Dystrophy, Duchenne / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D010805:Physical Conditioning, Animal / Q000502:physiology; D020442:Poloxamer / Q000494:pharmacology* / Q000627:therapeutic use; D012508:Sarcolemma / Q000187:drug effects* / Q000378:metabolism; D013501:Surface-Active Agents / Q000494:pharmacology / Q000627:therapeutic use; D017211:Treatment Failure
D004396:Coloring Agents; D013501:Surface-Active Agents; D020442:Poloxamer