Seventy-Five Percent Nephrectomy and the Disposition of Inorganic Mercury in 23-Dimercaptopropanesulfonic Acid-Treated Rats Lacking Functional Multidrug-Resistance Protein 2

摘要

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.