The interaction of chromium (VI) with macrophages

Depletion of glutathione and inhibition of glutathione reductase

A. Lalaouni, C.J. Henderson, C. Kupper, M.H. Grant

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

There are reports of alterations in the number and functions of the cells of the immune system in patients with metal-on-metal (MOM) orthopaedic implants. These effects have been correlated with elevated chromium levels in the patients' blood. We have investigated the interactions of clinically relevant concentrations of Cr VI with macrophages in vitro, and the mechanisms responsible for its toxicity. Cr VI causes a concentration dependent decrease in macrophage viability above 1 microM as measured by the MTT and Neutral Red assays. This falls well within the range of circulating chromium serum concentrations measured in patients with MOM. Intracellular reduced glutathione (GSH) levels fall as a result, and most of the loss (86%) is accounted for by oxidation to the dimer, GSSG. Prior depletion of GSH does not sensitise the cells to Cr VI toxicity, implying that it is not involved in protecting the cells against the effects of Cr VI. During the metabolism of Cr VI, glutathione reductase activity is inhibited. In contrast, the activities of catalase and superoxide dismutase are not significantly altered. Prior inhibition of glutathione reductase activity protects against the toxicity of Cr VI to a significant extent, suggesting that it reduces Cr VI to a toxic metabolite.
Original languageEnglish
Pages (from-to)76-81
Number of pages6
JournalToxicology
Volume236
Issue number1-2
DOIs
Publication statusPublished - 1 Jul 2007

Fingerprint

Glutathione Reductase
Macrophages
Glutathione
Metals
Toxicity
Chromium
Neutral Red
Glutathione Disulfide
Poisons
Immune system
Catalase
Orthopedics
Superoxide Dismutase
Metabolites
chromium hexavalent ion
Immune System
Metabolism
Dimers
Cell Count
Assays

Keywords

  • Chromium(VI) toxicity to macrophages
  • Inhibition of glutathione reductase
  • Depletion of glutathione
  • Cytoprotection
  • Metal-on-metal orthopaedic hip implants

Cite this

@article{cdc61200ddbe4fbca655907a795d44ee,
title = "The interaction of chromium (VI) with macrophages: Depletion of glutathione and inhibition of glutathione reductase",
abstract = "There are reports of alterations in the number and functions of the cells of the immune system in patients with metal-on-metal (MOM) orthopaedic implants. These effects have been correlated with elevated chromium levels in the patients' blood. We have investigated the interactions of clinically relevant concentrations of Cr VI with macrophages in vitro, and the mechanisms responsible for its toxicity. Cr VI causes a concentration dependent decrease in macrophage viability above 1 microM as measured by the MTT and Neutral Red assays. This falls well within the range of circulating chromium serum concentrations measured in patients with MOM. Intracellular reduced glutathione (GSH) levels fall as a result, and most of the loss (86{\%}) is accounted for by oxidation to the dimer, GSSG. Prior depletion of GSH does not sensitise the cells to Cr VI toxicity, implying that it is not involved in protecting the cells against the effects of Cr VI. During the metabolism of Cr VI, glutathione reductase activity is inhibited. In contrast, the activities of catalase and superoxide dismutase are not significantly altered. Prior inhibition of glutathione reductase activity protects against the toxicity of Cr VI to a significant extent, suggesting that it reduces Cr VI to a toxic metabolite.",
keywords = "Chromium(VI) toxicity to macrophages, Inhibition of glutathione reductase, Depletion of glutathione, Cytoprotection, Metal-on-metal orthopaedic hip implants",
author = "A. Lalaouni and C.J. Henderson and C. Kupper and M.H. Grant",
year = "2007",
month = "7",
day = "1",
doi = "10.1016/j.tox.2007.04.002",
language = "English",
volume = "236",
pages = "76--81",
journal = "Toxicology",
issn = "0300-483X",
number = "1-2",

}

The interaction of chromium (VI) with macrophages : Depletion of glutathione and inhibition of glutathione reductase. / Lalaouni, A.; Henderson, C.J.; Kupper, C.; Grant, M.H.

In: Toxicology, Vol. 236, No. 1-2, 01.07.2007, p. 76-81.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The interaction of chromium (VI) with macrophages

T2 - Depletion of glutathione and inhibition of glutathione reductase

AU - Lalaouni, A.

AU - Henderson, C.J.

AU - Kupper, C.

AU - Grant, M.H.

PY - 2007/7/1

Y1 - 2007/7/1

N2 - There are reports of alterations in the number and functions of the cells of the immune system in patients with metal-on-metal (MOM) orthopaedic implants. These effects have been correlated with elevated chromium levels in the patients' blood. We have investigated the interactions of clinically relevant concentrations of Cr VI with macrophages in vitro, and the mechanisms responsible for its toxicity. Cr VI causes a concentration dependent decrease in macrophage viability above 1 microM as measured by the MTT and Neutral Red assays. This falls well within the range of circulating chromium serum concentrations measured in patients with MOM. Intracellular reduced glutathione (GSH) levels fall as a result, and most of the loss (86%) is accounted for by oxidation to the dimer, GSSG. Prior depletion of GSH does not sensitise the cells to Cr VI toxicity, implying that it is not involved in protecting the cells against the effects of Cr VI. During the metabolism of Cr VI, glutathione reductase activity is inhibited. In contrast, the activities of catalase and superoxide dismutase are not significantly altered. Prior inhibition of glutathione reductase activity protects against the toxicity of Cr VI to a significant extent, suggesting that it reduces Cr VI to a toxic metabolite.

AB - There are reports of alterations in the number and functions of the cells of the immune system in patients with metal-on-metal (MOM) orthopaedic implants. These effects have been correlated with elevated chromium levels in the patients' blood. We have investigated the interactions of clinically relevant concentrations of Cr VI with macrophages in vitro, and the mechanisms responsible for its toxicity. Cr VI causes a concentration dependent decrease in macrophage viability above 1 microM as measured by the MTT and Neutral Red assays. This falls well within the range of circulating chromium serum concentrations measured in patients with MOM. Intracellular reduced glutathione (GSH) levels fall as a result, and most of the loss (86%) is accounted for by oxidation to the dimer, GSSG. Prior depletion of GSH does not sensitise the cells to Cr VI toxicity, implying that it is not involved in protecting the cells against the effects of Cr VI. During the metabolism of Cr VI, glutathione reductase activity is inhibited. In contrast, the activities of catalase and superoxide dismutase are not significantly altered. Prior inhibition of glutathione reductase activity protects against the toxicity of Cr VI to a significant extent, suggesting that it reduces Cr VI to a toxic metabolite.

KW - Chromium(VI) toxicity to macrophages

KW - Inhibition of glutathione reductase

KW - Depletion of glutathione

KW - Cytoprotection

KW - Metal-on-metal orthopaedic hip implants

U2 - 10.1016/j.tox.2007.04.002

DO - 10.1016/j.tox.2007.04.002

M3 - Article

VL - 236

SP - 76

EP - 81

JO - Toxicology

JF - Toxicology

SN - 0300-483X

IS - 1-2

ER -