Time course of the binding of platinum to subfractions of the kidney cytosol in the cisplatin-treated rat.

In male rats treated with cis-dichlorodiammine platinum II (cisplatin, 5 mg/kg, s.c.), the accumulation of Pt in the kidneys occurred in two phases. Total renal Pt content peaked after 15 min and decreased rapidly, then increased to a second peak after 48 hr and thereafter decreased slowly during the next 6 days. Sephadex G-50 chromatography showed that in the kidney cytosol Pt was located in three subfractions; a high molecular weight (HMW) fraction (relative elution volume, Vr = 0.9-1.2), a heterogeneous low molecular weight (LMW) Pt-binding fraction (Vr = 1.2-2.2) and a LMW complex fraction (Vr = 2.2-2.7). Initially, most of the Pt was located in the HMW- and LMW complex fractions and the initial loss of Pt from the cytosol occurred from the latter fraction. In contrast, during the second phase much of the additional Pt accumulated in the LMW Pt-binding fraction, the Pt content of which paralleled that in the whole kidney. It is suggested that the LMW Pt-binding fraction may play a significant role in the accumulation and retention of Pt and may provide a site of detoxification during the second phase of influx of Pt into the kidneys.