Ultrastructural and biochemical effects of D-penicillamine on mouse hepatocytes.

The ultrastructural and oxidative metabolic effects of D-penicillamine were examined in hepatocytes of mice fed various concentrations of the drug for periods up to 11 days. In virtually all animals studied, membranous material in the form of whorls, sheaves, and irregular networks was observed in some bile canaliculi. In several mice a few mitochondria were substantially enlarged, with diameters of 4-6 micron. In other animals some mitochondria became quite elongated, measuring 10 micron in length but only 0.5 micron in width. Certain mitochondria had small deposits of dense material in their outer compartment. Lysosomes contained numerous small dense particles; aggregates of these particles were also observed free in the cytosol. Despite these alterations, the vast majority of hepatocytes showed no changes whatsoever. Study of isolated hepatic mitochondria derived from the experimental animals showed no alterations in oxidative metabolism. It may be concluded that, unlike other copper-chelating agents, D-penicillamine has little significant morphological and biochemical effect on mouse hepatocytes, even when its concentration exceeds standard clinical dosages.