63Ni content of renal parenchyma and nuclei from 63NiCl2-treated rats

The time-course and dose-effect relationships for 63Ni uptake in renal parenchyma and nuclei were delineated in 63NiCl2-treated rats, based upon isolation of renal nuclei by sucrose gradient centrifugation and measurements of 63Ni by liquid scintillation counting. In 5 groups of rats killed 2 to 24 hours after 63NiCl2 injection (36 mumol/kg, im), 63Ni content of renal parenchyma (mean +/- SD) diminished from 3.0 +/- 0.3% of the dose at 2 hours to 0.9 +/- 0.3% of the dose at 24 hours; nuclear 63Ni content diminished from 10.5 +/- 4.4 pmol/10(6) nuclei at 2 hours to 3.0 +/- 0.3 pmol/10(6) nuclei at 24 hours. In 8 groups of rats killed 2 hours after injection of 63NiCl2 at dosages from 3 to 250 mumol/kg, 63Ni concentrations in renal nuclei increased progressively from 1.1 +/- 0.3 pmol/10(6) nuclei at 3 mumol/kg to 32.1 +/- 1.7 pmol/10(6) nuclei at 250 mumol/kg. Nuclear 63Ni content generally averaged 1.9 to 2.4% of total renal 63Ni; significantly higher mean values (3.4 +/- 1.0%) were observed in rats killed 48 hours after 5 daily injections of 63NiCl2 (1.1 mumol/kg/day). Combined administration of diethyldithiocarbamate (DDC, 1.33 mmol/kg, im) and 63NiCl2 (36 mumol/kg, im) increased 63Ni uptake in renal nuclei (4.8 +/- 1.4% of renal 63Ni; P less than 0.05 versus corresponding value of 2.0 +/- 0.2% in rats that received 63NiCl2, alone). Enhanced nuclear uptake of 63Ni evidently explains the synergistic effect of DDC and NiCl2 on induction of heme oxygenase activity in rat kidney.