UPTAKE AND METABOLISM OF CISPLATIN BY RAT-KIDNEY

Cisplatin, an effective antineoplastic agent, is toxic to the kidney. Since the kidney''s vulnerability to cisplatin may originate in its ability to accumulate and retain Pt to a greater degree than other organs, the characteristics of the renal accumulation of Pt and the nature of intracellular Pt were investigated. Cisplatin and ethylenediamminedichloroplatinum, nephrotoxic and antineoplastic liganded Pt compounds, were concentrated in rat renal cortical slices 5-fold above medium concentration. Pt uptake was energy and temperature-dependent and could be inhibited by drugs which inhibit base transport. The organic anions p-aminohippurate and pyrazinoate did not reduce renal slice Pt uptake. Unbound Pt in the blood and urine was predominantly cisplatin but unbound Pt in kidney cytosol was not. This latter compound, in contrast to cisplatin, was not active as a mutagen. The kidney may accumulate Pt in part by transport or specific binding to the base transport system in the kidney and biotransforms it intracellularly. Unbound Pt in the cell is not cisplatin and may no longer be toxic.