MRP2 and the handling of mercuric ions in rats exposed acutely to inorganic and organic species of mercury

Journal Article · Mon Feb 14 23:00:00 EST 2011 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2010.11.015· OSTI ID:21535237

Joshee, Lucy; Zalups, Rudolfs K

Mercuric ions accumulate preferentially in renal tubular epithelial cells and bond with intracellular thiols. Certain metal-complexing agents have been shown to promote extraction of mercuric ions via the multidrug resistance-associated protein 2 (MRP2). Following exposure to a non-toxic dose of inorganic mercury (Hg{sup 2+}), in the absence of complexing agents, tubular cells are capable of exporting a small fraction of intracellular Hg{sup 2+} through one or more undetermined mechanisms. We hypothesize that MRP2 plays a role in this export. To test this hypothesis, Wistar (control) and TR{sup -} rats were injected intravenously with a non-nephrotoxic dose of HgCl{sub 2} (0.5 {mu}mol/kg) or CH{sub 3}HgCl (5 mg/kg), containing [{sup 203}Hg], in the presence or absence of cysteine (Cys; 1.25 {mu}mol/kg or 12.5 mg/kg, respectively). Animals were sacrificed 24 h after exposure to mercury and the content of [{sup 203}Hg] in blood, kidneys, liver, urine and feces was determined. In addition, uptake of Cys-S-conjugates of Hg{sup 2+} and methylmercury (CH{sub 3}Hg{sup +}) was measured in inside-out membrane vesicles prepared from either control Sf9 cells or Sf9 cells transfected with human MRP2. The amount of mercury in the total renal mass and liver was significantly greater in TR{sup -} rats than in controls. In contrast, the amount of mercury in urine and feces was significantly lower in TR{sup -} rats than in controls. Data from membrane vesicles indicate that Cys-S-conjugates of Hg{sup 2+} and CH{sub 3}Hg{sup +} are transportable substrates of MRP2. Collectively, these data indicate that MRP2 plays a role in the physiological handling and elimination of mercuric ions from the kidney.

• OSTI ID: 21535237
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 1 Vol. 251; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
AMINO ACIDS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL MATERIALS
BIOLOGICAL WASTES
BODY
BODY FLUIDS
CARBOXYLIC ACIDS
CHARGED PARTICLES
CHELATING AGENTS
CHLORIDES
CHLORINE COMPOUNDS
CONTROL
CYSTEINE
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
DOSES
ELEMENTS
EVEN-ODD NUCLEI
FECES
GLANDS
HALIDES
HALOGEN COMPOUNDS
HEAVY NUCLEI
IONS
ISOTOPES
KIDNEYS
LIVER
MAMMALS
MATERIALS
MEMBRANES
MERCURY
MERCURY 203
MERCURY CHLORIDES
MERCURY COMPOUNDS
MERCURY HALIDES
MERCURY IONS
MERCURY ISOTOPES
METALS
METHYLMERCURY
NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC MERCURY COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
RADIOISOTOPES
RATS
RODENTS
THIOLS
URINE
VERTEBRATES
WASTES