Cr(VI) inhibits DNA, RNA and protein syntheses in hepatocytes: Involvement of glutathione reductase, reduced glutathione and DT-diaphorase

M. Gunaratnam, M.H. Grant

    Research output: Contribution to journalArticle

    17 Citations (Scopus)

    Abstract

    In patients with orthopaedic implants, metallic particles have been shown to be disseminated widely throughout the body, particularly in the liver, spleen and lymph nodes. Levels of metal particles and ions in distant organs were highest in patients with loose, corroded prostheses, and when stainless steel and cobalt chrome alloy corrode, chromium is released predominantly as Cr (VI), a toxic ion. This manuscript investigates the interaction of Cr (VI) with liver cells in terms of inhibition of macromolecular synthesis, and the contribution of reduced glutathione (GSH), DT-diaphorase and glutathione reductase (GRd) to the toxicity of Cr (VI). Cr (VI) caused concentration dependent inhibition of protein, DNA and RNA synthesis in hepatocytes. GRd and to a lesser extent DT-diaphorase activities were involved in the generation of toxic intermediates. GRd activity was markedly inhibited during the reduction of Cr (VI), and GSH levels decreased. The concentrations of Cr (VI) found to inhibit macromolecular syntheses in this study are clinically relevant: it is therefore important to develop implants with minimum wear potential.
    LanguageEnglish
    Pages879-886
    Number of pages7
    JournalToxicology in Vitro
    Volume22
    Issue number4
    DOIs
    Publication statusPublished - 2008

    Fingerprint

    NAD(P)H Dehydrogenase (Quinone)
    Glutathione Reductase
    Glutathione
    Hepatocytes
    RNA
    DNA
    Proteins
    Poisons
    Liver
    Chromium Alloys
    Ions
    Stainless Steel
    Orthopedics
    Cobalt
    Prosthetics
    Prostheses and Implants
    Toxicity
    chromium hexavalent ion
    Spleen
    Lymph Nodes

    Keywords

    • hexavalent chromium
    • macromolecular synthesis
    • hepatocytes
    • metallic debris
    • orthopaedic implants
    • bioengineering

    Cite this

    @article{c5923d8f8ba2454895f18612476301f6,
    title = "Cr(VI) inhibits DNA, RNA and protein syntheses in hepatocytes: Involvement of glutathione reductase, reduced glutathione and DT-diaphorase",
    abstract = "In patients with orthopaedic implants, metallic particles have been shown to be disseminated widely throughout the body, particularly in the liver, spleen and lymph nodes. Levels of metal particles and ions in distant organs were highest in patients with loose, corroded prostheses, and when stainless steel and cobalt chrome alloy corrode, chromium is released predominantly as Cr (VI), a toxic ion. This manuscript investigates the interaction of Cr (VI) with liver cells in terms of inhibition of macromolecular synthesis, and the contribution of reduced glutathione (GSH), DT-diaphorase and glutathione reductase (GRd) to the toxicity of Cr (VI). Cr (VI) caused concentration dependent inhibition of protein, DNA and RNA synthesis in hepatocytes. GRd and to a lesser extent DT-diaphorase activities were involved in the generation of toxic intermediates. GRd activity was markedly inhibited during the reduction of Cr (VI), and GSH levels decreased. The concentrations of Cr (VI) found to inhibit macromolecular syntheses in this study are clinically relevant: it is therefore important to develop implants with minimum wear potential.",
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    author = "M. Gunaratnam and M.H. Grant",
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    Cr(VI) inhibits DNA, RNA and protein syntheses in hepatocytes: Involvement of glutathione reductase, reduced glutathione and DT-diaphorase. / Gunaratnam, M.; Grant, M.H.

    In: Toxicology in Vitro, Vol. 22, No. 4, 2008, p. 879-886.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Cr(VI) inhibits DNA, RNA and protein syntheses in hepatocytes: Involvement of glutathione reductase, reduced glutathione and DT-diaphorase

    AU - Gunaratnam, M.

    AU - Grant, M.H.

    PY - 2008

    Y1 - 2008

    N2 - In patients with orthopaedic implants, metallic particles have been shown to be disseminated widely throughout the body, particularly in the liver, spleen and lymph nodes. Levels of metal particles and ions in distant organs were highest in patients with loose, corroded prostheses, and when stainless steel and cobalt chrome alloy corrode, chromium is released predominantly as Cr (VI), a toxic ion. This manuscript investigates the interaction of Cr (VI) with liver cells in terms of inhibition of macromolecular synthesis, and the contribution of reduced glutathione (GSH), DT-diaphorase and glutathione reductase (GRd) to the toxicity of Cr (VI). Cr (VI) caused concentration dependent inhibition of protein, DNA and RNA synthesis in hepatocytes. GRd and to a lesser extent DT-diaphorase activities were involved in the generation of toxic intermediates. GRd activity was markedly inhibited during the reduction of Cr (VI), and GSH levels decreased. The concentrations of Cr (VI) found to inhibit macromolecular syntheses in this study are clinically relevant: it is therefore important to develop implants with minimum wear potential.

    AB - In patients with orthopaedic implants, metallic particles have been shown to be disseminated widely throughout the body, particularly in the liver, spleen and lymph nodes. Levels of metal particles and ions in distant organs were highest in patients with loose, corroded prostheses, and when stainless steel and cobalt chrome alloy corrode, chromium is released predominantly as Cr (VI), a toxic ion. This manuscript investigates the interaction of Cr (VI) with liver cells in terms of inhibition of macromolecular synthesis, and the contribution of reduced glutathione (GSH), DT-diaphorase and glutathione reductase (GRd) to the toxicity of Cr (VI). Cr (VI) caused concentration dependent inhibition of protein, DNA and RNA synthesis in hepatocytes. GRd and to a lesser extent DT-diaphorase activities were involved in the generation of toxic intermediates. GRd activity was markedly inhibited during the reduction of Cr (VI), and GSH levels decreased. The concentrations of Cr (VI) found to inhibit macromolecular syntheses in this study are clinically relevant: it is therefore important to develop implants with minimum wear potential.

    KW - hexavalent chromium

    KW - macromolecular synthesis

    KW - hepatocytes

    KW - metallic debris

    KW - orthopaedic implants

    KW - bioengineering

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