Abstract
In the present study, we evaluated the disposition of inorganic mercury (Hg2+) 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 Hg2+ during renal insufficiency. All animals were treated with a low dose (0.5 μmol/kg i.v.) of mercuric chloride (HgCl2). At 24 and 28 h after exposure to HgCl2, matched groups of Wistar and TR− rats received normal saline or DMSA (intraperitoneally). Forty-eight hours after exposure to HgCl2, the disposition of Hg2+ was examined. A particularly notable effect of 75% nephrectomy in both strains of rats was enhanced renal accumulation of Hg2+, specifically in the outer stripe of the outer medulla. In addition, hepatic accumulation, fecal excretion, and blood levels of Hg2+ 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 Hg2+ in all rats. DMSA did not, however, affect hepatic content of Hg2+, 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 Hg2+ after a 75% reduction of renal mass.
Footnotes
This work was supported in part by the National Institutes of Health, National Institute of Environmental Health Sciences [Grants ES05980, ES015511] (to R.K.Z. and C.C.B., respectively).
Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
doi:10.1124/jpet.109.163774.
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ABBREVIATIONS:
- Hg2+
- inorganic mercury
- ABC
- ATP-binding cassette
- DMSA
- meso-2,3-dimercaptopropanesunccinc acid
- DMPS
- 2,3-dimercaptopropanesulfonic acid
- HgCl2
- mercuric chloride
- HgO
- mercuric oxide
- MRP2
- multidrug-resistance protein 2
- NPX
- nephrectomized
- OAT1
- organic anion transporter 1
- PAH
- para-aminohippuric acid
- SO
- sham-operated
- TR−
- transport-deficient
- PCR
- polymerase chain reaction.
- Received November 11, 2009.
- Accepted December 21, 2009.
- Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics
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