Righting ability and skeletal muscle properties of phenytoin-treated dystrophic chickens

Abstract

Chickens with an inherited muscular dystrophy (line 413) and genetically related normal controls (line 412) were treated with phenytoin (diphenylhydantoin, DPH) on Days 1 through 40 ex ovo. DPH (20 mg/kg, intraperitoneally, b.i.d.) and a combination of DPH and intermittent “exercise” (twice-daily testing of righting ability) beneficially affected muscle function, morphology, and biochemistry. DPH dramatically improved the righting ability of dystrophic chicks, and the exhaustion scores of many treated birds were still as high as those of normal chicks after 30 days of treatment. Muscles from chicks killed after 27 to 40 days of treatment had decreased fiber diameters, increased lactic dehydrogenase (LDH) activity, and reduced acetylcholinesterase and butyrylcholinesterase activities. The effects of DPH were more pronounced in the posterior latissimus dorsi than in the pectoral muscle and were potentiated by exercise. Exercise alone produced a transient increase in righting ability and increased LDH activity of dystrophic muscles. The abnormal, rounded appearance of dystrophic muscle fibers was not altered by treatments. Research reported elsewhere showed that DPH partially corrected abnormal electromyographic activity of dystrophic chicken muscles. The data presented here show that other symptoms of avian dystrophy are also alleviated by DPH and suggest that abnormal membrane activity plays an important role in this myopathy.