Seventy-five percent nephrectomy and the disposition of inorganic mercury in 2,3-dimercaptopropanesulfonic acid-treated rats lacking functional multidrug-resistance protein 2.

Abstract

In the present study, we evaluated the disposition of inorganic mercury (Hg(2+)) in sham-operated and 75% nephrectomized (NPX) Wistar and transport-deficient (TR(-)) rats treated with saline or the chelating agent meso-2,3-dimercaptosuccinic acid (DMSA). Based on previous studies, DMSA and TR(-) rats were used as tools to examine the potential role of multidrug-resistance protein 2 (MRP2) in the disposition of Hg(2+) during renal insufficiency. All animals were treated with a low dose (0.5 mumol/kg i.v.) of mercuric chloride (HgCl(2)). At 24 and 28 h after exposure to HgCl(2), matched groups of Wistar and TR(-) rats received normal saline or DMSA (intraperitoneally). Forty-eight hours after exposure to HgCl(2), the disposition of Hg(2+) was examined. A particularly notable effect of 75% nephrectomy in both strains of rats was enhanced renal accumulation of Hg(2+), specifically in the outer stripe of the outer medulla. In addition, hepatic accumulation, fecal excretion, and blood levels of Hg(2+) were enhanced in rats after 75% nephrectomy, especially in the TR(-) rats. Treatment with DMSA increased both the renal tubular elimination and urinary excretion of Hg(2+) in all rats. DMSA did not, however, affect hepatic content of Hg(2+), even in the 75% NPX TR(-) rats. We also show with real-time polymerase chain reaction that after 75% nephrectomy and compensatory renal growth, expression of MRP2 (only in Wistar rats) and organic anion transporter 1 is enhanced in the remaining functional proximal tubules. We conclude that MRP2 plays a significant role in the renal and corporal disposition of Hg(2+) after a 75% reduction of renal mass.

• Authors: Rudolfs K Zalups, Christy C Bridges
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 332 Issue 3 Pg. 866-75 (Mar 2010) ISSN: 1521-0103 [Electronic] United States
• PMID: 20032202 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Chelating Agents
• Multidrug Resistance-Associated Protein 2
• Multidrug Resistance-Associated Proteins
• Organic Anion Transport Protein 1
• Slc22a6 protein, rat
• Unithiol
• Mercuric Chloride

Topics

• Animals
• Chelating Agents (pharmacology)
• Epithelial Cells (metabolism)
• Kidney (drug effects, metabolism)
• Kidney Tubules, Proximal (metabolism)
• Male
• Mercuric Chloride (blood, pharmacokinetics, urine)
• Multidrug Resistance-Associated Protein 2
• Multidrug Resistance-Associated Proteins (biosynthesis, genetics)
• Nephrectomy (adverse effects)
• Organic Anion Transport Protein 1 (biosynthesis)
• Rats
• Rats, Mutant Strains
• Rats, Wistar
• Unithiol (pharmacology)
• Urothelium (metabolism)