title: Utilization of renal slices to evaluate the efficacy of chelating agents for removing mercury from the kidney.
abstract: Mercury is an environmental contaminant that preferentially accumulates in the kidney. It has been previously shown using proton-induced X-ray emission analysis that mercury (HgCl2) accumulated in precision-cut rabbit renal cortical slices. In this study, the efficacy of seven chelating agents for the removal of Hg from renal slices has been examined. Rabbits were injected with HgCl2 (10 mg/kg) and 3 h later kidneys were sliced, or renal slices were exposed in vitro to a mildly toxic concentration of HgCl2 (5 x 10(-5)M, 4 h). The slices were then treated in vitro with 10 mM concentrations of EDTA, lipoic acid (LA), penicillamine (PA), glutathione (GSH), 1,4-dithiothreitol (DTT), DMSA, or DMPS. DMPS proved to be the most effective in mobilizing Hg from in vivo or in vitro HgCl2-exposed renal tissue ( > 85% of control after 3 h incubation). Relative efficacies for the seven agents were DMPS > DMSA, PA > DTT, GSH > LA, EDTA. The use of renal slices appears to be a useful in vitro tool for assessing the efficacy of chelating agents on mobilizing accumulated Hg from renal tissue.
authors.affiliation: Center for Toxicology, The University of Arizona, Tucson 85721, USA.
authors.forename: R L
authors.initials: RL
authors.lastname: Keith
authors.forename: I
authors.initials: I
authors.lastname: Setiarahardjo
authors.forename: Q
authors.initials: Q
authors.lastname: Fernando
authors.forename: H V
authors.initials: HV
authors.lastname: Aposhian
authors.forename: A J
authors.initials: AJ
authors.lastname: Gandolfi
mesh_terms: D000818:Animals; D000931:Antidotes / Q000493:pharmacokinetics / Q000633:toxicity*; D002614:Chelating Agents / Q000494:pharmacology* / Q000633:toxicity; D004229:Dithiothreitol / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D004492:Edetic Acid / Q000494:pharmacology; D005069:Evaluation Studies as Topic; D005978:Glutathione / Q000494:pharmacology; D007668:Kidney / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008627:Mercuric Chloride / Q000008:administration & dosage; D008628:Mercury / Q000378:metabolism* / Q000633:toxicity*; D010396:Penicillamine / Q000494:pharmacology; D011817:Rabbits; D004113:Succimer / Q000494:pharmacology; D008063:Thioctic Acid / Q000494:pharmacology; D014494:Unithiol / Q000494:pharmacology
chemical_list: D000931:Antidotes; D002614:Chelating Agents; D014494:Unithiol; D008627:Mercuric Chloride; D008063:Thioctic Acid; D004492:Edetic Acid; D004113:Succimer; D008628:Mercury; D005978:Glutathione; D010396:Penicillamine; D004229:Dithiothreitol