Subcellular Distribution of Cadmium in Rat Liver on Repeated cadmium Administration

Abstract

The distribution pattern of cadmium in the liver, when renal damage occurred, was studied. Twenty Wistar male rats were divided into four injection dose groups of 0, 0.3, 1.0, and 1.5 mg of Cd (as CdCl2) per kg of body weight. Subcutaneous injections were given 6 days a week. At 4 weeks, renal damage in the 1.0-and 1.5-mg dose groups occurred in the form of glucosuria, amino aciduria, or proteinuria. Amount of cadmium in the liver increased with dosage and appeared to reach a near-maximum in the 1.0-mg dose group. The hepatic Cd/Zn ratio increased in proportion to the tissue cadmium concentration but the plotted value in the 1.5-mg dose group was extremely higher than the value expected from the increase rate up to 1.0-mg dose group. The liver tissues were homogenized separately in 4 volumes of cold 0.25 M sucrose and the homogenate was centrifuged at 27000×g for 60 min. Increased dosage of cadmium resulted in an increase in the accumulation of cadmium in the 27000×g sediment, which may contain nuclei, mitochondria, lysosomes, and heavy microsomes. The 27000×g supernatant was fractionated on Sephadex G-75. In the 0.3-mg dose group, most of cadmium in the supernatant was bound solely to metallothionein, a low molecular weight protein. In the 1.0-and 1.5-mg dose groups, most of the increased cadmium was bound to metallothionein, but four additional fractions of cadmium appeared. One of them had properties similar to metallothionein. Metallothionein has a molecular weight of approximately 11000 and one of the additional fractions had a molecular weight of approximately 19900, and was assumed to be a dimer of metallothionein.