Chronic Dosing with Membrane Sealant Poloxamer 188 NF Improves Respiratory Dysfunction in Dystrophic <i>Mdx and Mdx/Utrophin<sup>-/-</sup></i> Mice


<div><p>Poloxamer 188 NF (national formulary (NF) grade of P-188) improves cardiac muscle function in the <i>mdx</i> mouse and golden retriever muscular dystrophy models. However <i>in vivo</i> effects on skeletal muscle have not been reported. We postulated that P-188 NF might protect diaphragm muscle membranes from contraction-induced injury in <i>mdx</i> and mdx/utrophin<sup>-/-</sup> (dko) muscular dystrophy models. In the first study 7-month old <i>mdx</i> mice were treated for 22 weeks with subcutaneous (s.c.) injections of saline or P-188 NF at 3 mg/Kg. In the second, dkos were treated with saline or P-188 NF (1 mg/Kg) for 8 weeks beginning at age 3 weeks. Prednisone was the positive control in both studies. Respiratory function was monitored using unrestrained whole body plethysmography. P-188 NF treatment affected several respiratory parameters including tidal volume/BW and minute volume/BW in mdx mice. In the more severe dko model, P-188 NF (1 mg/Kg) significantly slowed the decline in multiple respiratory parameters compared with saline-treated dko mice. Prednisone’s effects were similar to those seen with P-188 NF. Diaphragms from P-188 NF or prednisone treated <i>mdx</i> and dko mice showed signs of muscle fiber protection including less centralized nuclei, less variation in fiber size, greater fiber density, and exhibited a decreased amount of collagen deposition. P-188 NF at 3 mg/Kg s.c. also improved parameters of systolic and diastolic function in <i>mdx</i> mouse hearts. These results suggest that P-188 NF may be useful in treating respiratory and cardiac dysfunction, the leading causes of death in Duchenne muscular dystrophy patients.</p></div

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oai:figshare.com:article/1504220Last time updated on 2/12/2018

This paper was published in FigShare.

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