Basolateral Uptake of Inorganic Mercury in the Kidney

Abstract

Renal disposition of administered inorganic mercury was studied in rats that had undergone an acute bilateral ureteral ligation shortly before being injected with a nontoxic 0.5-μmol/kg iv dose of inorganic mercury with or without 2.0 μmol/kg glutathione (GSH) or cysteine. Ureteral ligation and induction of “stop–flow” conditions were carried out to decrease glomerular filtration rate to negligible levels prior to the administration of inorganic mercury. The disposition of mercury was studied in the kidneys, liver, and blood 1 h after treatment. In rats given only mercuric chloride, the renal burden of mercury was approximately 20–25% of the administered dose of mercury, which is approximately 50% of the renal burden of mercury detected on average in normal rats. Coadministration of inorganic mercury with GSH or cysteine caused a significant increase in the renal uptake of mercury 1 h after treatment. The enhanced uptake of mercury in the kidneys was due to increased uptake of mercury in the renal cortex and outer stripe of the outer medulla. Pretreatment withpara-aminohippuric acid caused significant reductions in the renal concentration and burden of inorganic mercury in all the rats administered inorganic mercury, regardless of whether the inorganic mercury was coadministered with GSH or cysteine. Overall, the findings from the present study provide additional evidence that there is basolateral uptake of inorganic mercury in the kidneys and that the primary mechanism involved in this basolateral uptake is dependent on the activity of the organic anion transporter. More importantly, the present findings also show that GSH and cysteine enhance the basolateral uptake of mercuric ions in the kidney when they are coadministered with inorganic mercury (presumably in the form of mercuric conjugates). On the basis of the present findings, one is led to believe that mercuric conjugates of GSH and cysteine are taken up at the basolateral membrane following exposure to inorganic forms of mercury.