Effect of D-penicillamine on glomerular basement membrane, urinary N-acetyl-beta-D-glucosaminidase and protein excretion in rats.

The administration of D-penicillamine (450 mg/kg) to young rats resulted in an immediate increase in urinary NAG and volume, as well as mild proteinuria of a predominently low molecular weight type. Doses less than 400 mg/kg failed to alter the urinary profile. Analysis of glomerular basement membrane prepared from rats injected with D-penicillamine (450 mg/kg) failed to show any abnormalities in amino acid and sugar composition. In contrast, glomerular basement membrane prepared from D-penicillamine injected rats was more soluble than membrane prepared from normal rats in SDS and 2-mercaptoethanol. The solubilised components of the membrane were resolved on SDS-polyacrylamide gel electrophoresis. An increase in the low molecular weight, and a concomitant fall in the higher molecular weight components present in the membrane was demonstrated. D-penicillamine therefore affects glomerular basement membrane directly in young rats, possibly by interfering with cross-link formation. These studies may provide a further basis for the study of D-penicillamine toxicity in man.