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) e xpressed as tissue slice-to-medium ratio was used as a model to predict nep hrotoxicity of different nickel compounds. Pretreatment with nickel compoun ds for a period of up to 4 h was followed by an incubation with 74 muM PAH for 2 h. The PAH uptake by renal cortical slices was reduced by nickel comp ounds in both concentration- and time-dependent manner. Furthermore. the ex tent of such reduction of PAH uptake was found to depend on the chemical fo rm (speciation) of nickel. Thus, slice-to-medium ratios were 41, 49, 48, an d 66% of control values after a 4-h pretreatment with 0.378 mM nickel carbo nate hydroxide. 1.5 mM nickel subsulfide. 4 mM nickel Sulfate and 2.98 mM n ickel 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 > n ickel sulfate > nickel oxide. Treatment of renal cortical slices with high concentrations of either mannitol. a hydroxyl radical scavenger, or glutath ione significantly reduced the inhibition of PAH uptake by soluble form of nickel subsulfide, with concomitant reduction of nickel ion uptake by corti cal slices. But no such oxidative stress seems to be involved in nickel car bonate hydroxide-induced inhibition of PAH uptake. (C) 2001 Elsevier Scienc e Ireland Ltd. All rights reserved.