Studies on the copper and zinc content of the rat kidney after treatment with cisplatin.

The administration of cis-dichlorodiammine platinum II (cisplatin), at a dose of 5 mg/kg, subcutaneously (s.c.), to adult male Wistar rats, inhibited the normal accumulation of Cu and Zn in the kidneys. Cisplatin also produced a small increase in the concentration of Cu in the brain but had no significant effect on total Cu and Zn concentrations in the heart, thymus, liver, intestine, spleen, testes and muscle. Treatment of rats with 2 mg Cu2+/kg, intraperitoneally (i.p.), increased the renal Cu content whilst cisplatin pretreatment inhibited the uptake of Cu by the kidneys. The administration of cisplatin to the Cd2+-pretreated rat decreased the content of metallothionein-bound Cu in parallel with a reduction in total renal Cu content, but had no significant effect on the total renal content of Cd and Zn. Pretreatment with cisplatin decreased the subsequent uptake of Cd by 42% in the whole kidney and by 23% in the metallothionein fraction, but failed to reduce the Cd2+-induced accumulation of Cu in the kidneys. The significance of these observations in relation to the possible mechanism of the cisplatin-induced change in the Cu and Zn content of the kidney is discussed.