Glutathione effects on toxicity and uptake of mercuric chloride and sodium arsenite in rabbit renal cortical slices

C. A. Burton; K. Hatlelid; K. Divine; D. E. Carter; Q. Fernando; K. Brendel; A. J. Gandolfi

doi:10.1289/ehp.95103s181

Glutathione effects on toxicity and uptake of mercuric chloride and sodium arsenite in rabbit renal cortical slices

C. A. Burton, K. Hatlelid, K. Divine, D. E. Carter, Q. Fernando, K. Brendel, A. J. Gandolfi

Research output: Contribution to journal › Article › peer-review

40 Scopus citations

Abstract

The mechanism of renal uptake of nephrotoxic heavy metals such as HgCl₂ and NaAsO₂ is not clear. The metals are known to react with endogenous sulfhydryls such as glutathione (GSH), so metal-GSH conjugates may be delivered to the kidney. To study this possibility, renal cortical slices from male New Zealand white rabbits were incubated with 10^-4 M HgCl₂ or 10^-3 M NaAsO₂ ± stoichiometric amounts (1-3x) of GSH; or synthetic metal-GSH conjugates [10^-4 M Hg(SG)₂ or 10^-3 M As(SG)₃]. Incubations were performed at 37°C in DME-F12 buffer (95/5 O₂/CO₂) for 8 hr. Hg(SG)₂ reduced slice K⁺/DNA content, as an indicator of viability, significantly less than HgCl₂. As(SG)₃ exhibited a 2-hr delay in K⁺/DNA content reduction compared to NaAsO₂. This delay in toxicity was not correlated to changes in uptake. Arsenic and mercury accumulation, determined by proton-induced X-ray emission, were also identical between the metal salts and the metal-GSH conjugates. Exogenous GSH decreased HgCl₂ cytotoxicity and was correlated to a decrease in Hg accumulation in the slice. Exogenous GSH had limited if any protective effects against cytotoxicity by NaAsO₂ and a decrease in As accumulation was not observed. Complex metal-GSH interactions appear to exist and impact on the uptake and toxicity of these metals.

Original language	English (US)
Pages (from-to)	81-84
Number of pages	4
Journal	Environmental health perspectives
Volume	103
Issue number	SUPPL. 1
DOIs	https://doi.org/10.1289/ehp.95103s181
State	Published - 1995

Keywords

Arsenite
Glutathione
Mercuric chloride
Metal accumulation
Metal toxicity
Metals
Nephrotoxicity
Tissue slices

ASJC Scopus subject areas

Public Health, Environmental and Occupational Health
Health, Toxicology and Mutagenesis

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10.1289/ehp.95103s181

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@article{39a9675651854764b87ff8db79cbab14,

title = "Glutathione effects on toxicity and uptake of mercuric chloride and sodium arsenite in rabbit renal cortical slices",

abstract = "The mechanism of renal uptake of nephrotoxic heavy metals such as HgCl2 and NaAsO2 is not clear. The metals are known to react with endogenous sulfhydryls such as glutathione (GSH), so metal-GSH conjugates may be delivered to the kidney. To study this possibility, renal cortical slices from male New Zealand white rabbits were incubated with 10-4 M HgCl2 or 10-3 M NaAsO2 ± stoichiometric amounts (1-3x) of GSH; or synthetic metal-GSH conjugates [10-4 M Hg(SG)2 or 10-3 M As(SG)3]. Incubations were performed at 37°C in DME-F12 buffer (95/5 O2/CO2) for 8 hr. Hg(SG)2 reduced slice K+/DNA content, as an indicator of viability, significantly less than HgCl2. As(SG)3 exhibited a 2-hr delay in K+/DNA content reduction compared to NaAsO2. This delay in toxicity was not correlated to changes in uptake. Arsenic and mercury accumulation, determined by proton-induced X-ray emission, were also identical between the metal salts and the metal-GSH conjugates. Exogenous GSH decreased HgCl2 cytotoxicity and was correlated to a decrease in Hg accumulation in the slice. Exogenous GSH had limited if any protective effects against cytotoxicity by NaAsO2 and a decrease in As accumulation was not observed. Complex metal-GSH interactions appear to exist and impact on the uptake and toxicity of these metals.",

keywords = "Arsenite, Glutathione, Mercuric chloride, Metal accumulation, Metal toxicity, Metals, Nephrotoxicity, Tissue slices",

author = "Burton, {C. A.} and K. Hatlelid and K. Divine and Carter, {D. E.} and Q. Fernando and K. Brendel and Gandolfi, {A. J.}",

year = "1995",

doi = "10.1289/ehp.95103s181",

language = "English (US)",

volume = "103",

pages = "81--84",

journal = "Environmental health perspectives",

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T1 - Glutathione effects on toxicity and uptake of mercuric chloride and sodium arsenite in rabbit renal cortical slices

AU - Burton, C. A.

AU - Hatlelid, K.

AU - Divine, K.

AU - Carter, D. E.

AU - Fernando, Q.

AU - Brendel, K.

AU - Gandolfi, A. J.

PY - 1995

Y1 - 1995

N2 - The mechanism of renal uptake of nephrotoxic heavy metals such as HgCl2 and NaAsO2 is not clear. The metals are known to react with endogenous sulfhydryls such as glutathione (GSH), so metal-GSH conjugates may be delivered to the kidney. To study this possibility, renal cortical slices from male New Zealand white rabbits were incubated with 10-4 M HgCl2 or 10-3 M NaAsO2 ± stoichiometric amounts (1-3x) of GSH; or synthetic metal-GSH conjugates [10-4 M Hg(SG)2 or 10-3 M As(SG)3]. Incubations were performed at 37°C in DME-F12 buffer (95/5 O2/CO2) for 8 hr. Hg(SG)2 reduced slice K+/DNA content, as an indicator of viability, significantly less than HgCl2. As(SG)3 exhibited a 2-hr delay in K+/DNA content reduction compared to NaAsO2. This delay in toxicity was not correlated to changes in uptake. Arsenic and mercury accumulation, determined by proton-induced X-ray emission, were also identical between the metal salts and the metal-GSH conjugates. Exogenous GSH decreased HgCl2 cytotoxicity and was correlated to a decrease in Hg accumulation in the slice. Exogenous GSH had limited if any protective effects against cytotoxicity by NaAsO2 and a decrease in As accumulation was not observed. Complex metal-GSH interactions appear to exist and impact on the uptake and toxicity of these metals.

AB - The mechanism of renal uptake of nephrotoxic heavy metals such as HgCl2 and NaAsO2 is not clear. The metals are known to react with endogenous sulfhydryls such as glutathione (GSH), so metal-GSH conjugates may be delivered to the kidney. To study this possibility, renal cortical slices from male New Zealand white rabbits were incubated with 10-4 M HgCl2 or 10-3 M NaAsO2 ± stoichiometric amounts (1-3x) of GSH; or synthetic metal-GSH conjugates [10-4 M Hg(SG)2 or 10-3 M As(SG)3]. Incubations were performed at 37°C in DME-F12 buffer (95/5 O2/CO2) for 8 hr. Hg(SG)2 reduced slice K+/DNA content, as an indicator of viability, significantly less than HgCl2. As(SG)3 exhibited a 2-hr delay in K+/DNA content reduction compared to NaAsO2. This delay in toxicity was not correlated to changes in uptake. Arsenic and mercury accumulation, determined by proton-induced X-ray emission, were also identical between the metal salts and the metal-GSH conjugates. Exogenous GSH decreased HgCl2 cytotoxicity and was correlated to a decrease in Hg accumulation in the slice. Exogenous GSH had limited if any protective effects against cytotoxicity by NaAsO2 and a decrease in As accumulation was not observed. Complex metal-GSH interactions appear to exist and impact on the uptake and toxicity of these metals.

KW - Arsenite

KW - Glutathione

KW - Mercuric chloride

KW - Metal accumulation

KW - Metal toxicity

KW - Metals

KW - Nephrotoxicity

KW - Tissue slices

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DO - 10.1289/ehp.95103s181

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AN - SCOPUS:0028965802

SN - 0091-6765

VL - 103

SP - 81

EP - 84

JO - Environmental health perspectives

JF - Environmental health perspectives

IS - SUPPL. 1

ER -

Glutathione effects on toxicity and uptake of mercuric chloride and sodium arsenite in rabbit renal cortical slices

Abstract

Keywords

ASJC Scopus subject areas

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