The failure of supplemental dietary copper to prevent cuprizone-induced alterations in mouse hepatocytes

Weaning mice were fed a powdered complete diet containing either 0.5% cuprizone, 0.5% cuprizone + 0.01% copper sulfate, or 0.01% copper sulfate. With cuprizone as the sole additive, hepatic mitochondria became greatly enlarged. When the diet contained cuprizone + copper sulfate, giant mitochondria were still present, and, in addition, numerous lysosome-like structures became evident. When only copper sulfate was added to the normal diet, the mitochondria were of normal size, but the hepatocytes contained abundant lysosomes. Dietary supplementation with cuprizone or with cuprizone + copper sulfate resulted in considerably depressed (20-50%) rates of mitochondrial oxidation. Supplementation solely with copper sulfate produced virtually no changes in oxidative activity. It may be concluded that the subcellular effects of cuprizone are not based on its ability to produce copper deficiency by chelation of copper, but on other properties of this drug.