Differential role of metallothionein on Zn, Cd and Cu accumulation in hepatic cytosol of rats.

To examine the role of metallothionein (MT) on heavy metal accumulation in hepatic cytosol of rats, this study was carried out to determine the relative Zn, Cd and Cu-binding capacities of MT in hepatic cytosol of Zn, Cd and Cu-injected rats, respectively. The heavy metal contents were detected in the liver and cytosol in the following proportions: 65.2-74.8% of the Zn content, 61.9-65.6% of the Cu content, and approx. 65% of the Cd content. Each rat was given a single intraperitoneal injection of saline, ZnSO4 (1, 5, 10 and 20 mg Zn/kg b.w.), CuSO4 (2, 4 and 6 mg Cu/kg b.w.) or CdCl2 (1, 2 and 3 mg Cd/kg b.w.). The amounts of the increased Zn and Cu were attributable to MT and high molecular weight proteins, while most of the increased Cd was attributable to MT. There was a close relationship between heavy metal content of the cytosol and MT in all heavy metal-injected rats. Our data demonstrated that approx. 60% of the increased Zn or Cu in the hepatic cytosol of Zn or Cu-injected rats was bound to MT, while 83% of the increased Cd in hepatic cytosol of Cd-injected rats was bound to MT. Therefore the order of relative binding capacity in vivo of MT determined for several metals (Cd > Zn > Cu) did not correlate with the published in vitro order of affinity to MT, Cu > Cd > Zn. These results suggested that the role of MT in Zn or Cu accumulation in the liver of Zn or Cu-injected rats was different from that of MT in Cd accumulation in the liver of Cd-injected rats.