Studies on the toxicity of copper. I. The toxic action of copper in vivo and in vitro

Abstract

With the object of throwing light upon the brain damage found in patients with Wilson’s disease (hepato-lenticular degeneration) due to the accumulation of copper, the effect of Cu²⁺ has been investigated in pigeons. Subarachnoid injections of Cu²⁺ (10 to 25 µg) led to rapid onset of convulsions and death. These concentrations of Cu²⁺ inhibited pigeon and rat b rain mitochondria; more organized tissue breis or slices showed no significant inhibition of oxygen up take at Cu⁺²concentration inducing convulsions in vivo. Studies with radioactive copper (⁶⁴Cu) showed that the injected copper was widely distributed in the brain, though maximal near the site of injection. Centrifugation showed a high specific activity in the ATP-ase-rich microsomal fraction. Thorium in concentrations similar to Cu²⁺ was not toxic. From this we suggest that the Cu²⁺ does not alter the charge on some membrane surface. Since the effect of the copper is immediate, and since it does not affect respiration of slices in these low concentrations, we conclude that it is exerting its convulsive effect directly upon the cell surfaces.