Penicillamine effects on enzyme efflux from skeletal and heart muscle

We have previously shown that pretreatment of mice with diethylstilbestrol (DES) or prednisolone (Pr) lowered enzyme efflux from isolated mouse skeletal muscle. These same agents also lowered the high serum enzyme activities in boys with Duchenne's muscular dystrophy (DMD). In a continuing search for other agents with similar effects, the influence of penicillamine (Pe) on enzyme efflux from isolated muscle was assessed, because it lowered the high plasma creatine phosphokinase (CPK) and produce beneficial effects in avian muscular dystrophy. Three groups of mice received 0, 1, or 10 mg Pe daily for 14 days. All mice were given supplementary pyridoxine. The egress of CPK and lactate dehydrogenase from the isolated left gastrocnemius and heart was determined over a 5 hour period. Pe produced more modest effects than did DES or Pr. The 10 mg dose reduced enzyme efflux from the gastrocnemius by 10%. In contrast, heart enzyme efflux was augmented by 20%. Similar dose-related disparate effects on enzyme efflux from skeletal muscle and heart have been previously noted for DES and Pr. Pe is the third agent found to lower the high serum enzyme activities in muscular dystrophy and reduce gastrocnemius enzyme efflux from isolated mouse skeletal muscle. This further establishes the usefulness of the mouse assay for identifying agents that lower the high serum enzyme activities in muscular dystrophy.