Role of Intracellular Granules of Liver on Copper Metabolism

Biochemical examination and electron microscopic observation

Abstract

Male mice were given either one intraperitoneal injection of copper (25μmol CuSO₄⋅5H₂O/kg body weight) or one injection daily for seven days in order to determine copper metabolism in the liver. Copper contents in whole livers, bile and subcellular liver fractions were measured and the copper in liver cell granules was determined by electron X-ray microanalysis.
The results were as follows:
1) Absorbed copper was incorporated into soluble, lysosomal and peroxisomal fractions of the liver and released from the peroxisomal fraction within 24hrs after one injection of copper. Moreover, copper content in the bile increased. Excessive copper was found to be incorporated into the peroxisomal fraction at high levels as measured 24hrs after the termination of daily injections for seven days.
2) Electron microscopy revealed greater numbers of lysosomes and large dense bodies in both pericanalicular and perinuclear regions in livers which had received seven copper injections when compared to controls. Electron X-ray microanalysis further demonstrated that excessive copper was detectable in the large dense bodies, but not in peroxisomes.
The results demonstrate that excessive copper in the liver is incorporated into both the lysosomes and large dense bodies contained in the peroxisomal fraction and then excreted into the bile, and suggest that the large dense bodies play an important role in the metabolism of copper in liver cells.