Skeletal muscle protein loss due to D-penicillamine results from reduced protein synthesis

Reports in the literature indicate that (lie trifunctional amino acid D-pen icillamine (D-P) induces a variety of muscle abnormalities, although the me chanisms are unknown. We hypothesised that defects may also arise due to th e effects of D-P on rates of protein synthesis, possibly via changes in mus cle metal composition. Male Wistar rats were injected with D-P at doses of 50 and 500 mg/kg body weight, i.p. Rats designated as controls were injecte d with 0.15 mol/l NaCl. After 24 h, there were reductions in muscle protein contents, protein synthetic capacities (RNA:protein ratio), fractional rat es of protein synthesis, synthesis rates per unit RNA and synthesis rates p er unit DNA in skeletal muscles of D-P treated rats. There were no statisti cally significant differences between the responses of the muscles containi ng a predominance of either Type I (represented by the soleus) or Type II ( represented by the plantaris fibres. In general, intracellular amino acids were not significantly affected by D-P treatment. Changes in muscle metals included significant reductions in copper, iron and manganese, without alte rations in zinc or magnesium. In liver D-P reduced copper and iron though z inc, manganese and magnesium were unaffected. These effects of D-P on muscl e may have been direct, as plasma indices of liver (activities of alkaline phosphatase and alanine amino transferase) and kidney (urea, creatinine and electrolytes) damage were not significantly altered by D-P treatment. Plas ma levels of corticosterone, insulin and free T-3 were also not significant ly affected by D-P treatment. Muscle protein carbonyl concentrations, an in dex of free radical activity, were similarly unaffected. This is the first report of reduced rates of muscle protein synthesis in D-P treatment. Our d ata suggests that the reduced rates of muscle protein synthesis may contrib ute to, or reflect, the muscle abnormalities observed in patients undergoin g D-P treatment. (C) 2001 Elsevier Science Ltd. Ali rig-hts reserved.