Pretreatment with p-aminohippurate inhibits the renal uptake and accumulation of injected inorganic mercury in the rat

Abstract

The effects of intravenous pretreatment with the organic anion p-aminohippurate (PAH) on the disposition of intravenously administered inorganic mercury in the kidneys, liver and blood were evaluated in rats. In dose-response experiments, the renal uptake (and/or accumulation) of mercury, 1 h after the injection of a nontoxic 0.5 μmol/kg dose of mercuric chloride (HgCl 2), was significantly reduced in rats when a 1.0, 3.3 or 10 mmol/kg dose of PAH was administered 5 min prior to the injection of HgCl 2. This reduction was due to reduced uptake of mercury in both the renal cortex and outer stripe of the outer medulla. Near maximal inhibition appeared to be achieved with the 10 mmol/kg dose of PAH. Inhibition of the uptake (and/or accumulation) of mercury in the renal cortex and outer stripe of the outer medulla, 1 h after the injection of the nontoxic dose of HgCl 2, was also detected in experiments where HgCl 2 was injected 5, 30, 60 or 180 min after pretreatment with a 10 mmol/kg dose of PAH. The renal uptake of mercury was inhibited significantly when the nontoxic dose of inorganic mercury was administered 5, 30 or 60, but not 180 min after pretreatment with the 10 mmol/kg dose of PAH. In another experiment, the renal burden of mercury was significantly reduced for 24 h when pretreatment with a 10 mmol/kg dose of PAH was administered 5 min prior to the injection of HgCl 2. Pretreatment with PAH did not have an effect on the hepatic disposition of mercury, but it did cause a significant increase in the fraction of mercury present in the plasma of blood. In summary, the findings in the present study indicate that pretreatment with PAH inhibits the renal uptake of injected inorganic mercury in a dose-dependent and time-dependent manner. In addition, the findings tend to indicate that some fraction of the mercury that enters into renal tubular epithelial cells is by a mechanism involving the organic anion transport system.