Interactions of cis-platinum with cellular zinc and copper in rat liver and kidney tissues

Abstract

In the present study the effects of cis-diamminedichloroplatinum II (cis-DDP) on tissue and subcellular concentrations of endogenous Zn and Cu was investigated in liver and kidneys of rats injected i.p. with 5 mg/kg of cis-DDP. The binding of Pt to cytosolic ligands and its effect on Zn and Cu binding was also investigated. cis-DDP significantly reduced cellular Zn (20%) and Cu (23%) levels particularly in the kidneys. Intracellularly, these decreases were largely reflected in the corresponding cytosolic fractions, with 64% decrease in Zn and 56% in Cu concentrations. At 24 h following cis-DDP injection, in both liver and kidneys, about 50% of cytosolic Pt was present as low molecular weight (LMW) species and the remainder as protein-bound. A small proportion of cellular Pt was bound to a metallothionein-like protein in the liver as well as the kidneys. The binding of renal Zn to cytosolic proteins and LMW Zn-binding ligands was significantly decreased by cis-DDP. In the liver cytosol, there was a marked redistribution of Zn and Cu from LMW Zn/Cu-binding ligand to the MT-like proteins.