Effects of different nickel compounds on the transport of para-aminohippurate ion by rat renal cortical slices.

In vitro rat renal cortical slice uptake of para-aminohippurate ion (PAH) expressed as tissue slice-to-medium ratio was used as a model to predict nephrotoxicity of different nickel compounds. Pretreatment with nickel compounds for a period of up to 4 h was followed by an incubation with 74 microM PAH for 2 h. The PAH uptake by renal cortical slices was reduced by nickel compounds in both concentration- and time-dependent manner. Furthermore, the extent of such reduction of PAH uptake was found to depend on the chemical form (speciation) of nickel. Thus, slice-to-medium ratios were 41, 49, 48, and 66% of control values after a 4-h pretreatment with 0.378 mM nickel carbonate hydroxide, 1.5 mM nickel subsulfide, 4 mM nickel sulfate and 2.98 mM nickel oxide, respectively. Such an inhibition of PAH transport was not due to cytotoxicity. The results suggest that the nephrotoxic potency decreases in the following order: nickel carbonate hydroxide>nickel subsulfide>nickel sulfate>nickel oxide. Treatment of renal cortical slices with high concentrations of either mannitol, a hydroxyl radical scavenger, or glutathione significantly reduced the inhibition of PAH uptake by soluble form of nickel subsulfide, with concomitant reduction of nickel ion uptake by cortical slices. But no such oxidative stress seems to be involved in nickel carbonate hydroxide-induced inhibition of PAH uptake.