The role of glutathione reductase in the cytotoxicity of chromium (VI) in isolated rat hepatocytes

M. Gunaratnam, M.H. Grant

    Research output: Contribution to journalArticle

    30 Citations (Scopus)

    Abstract

    Chromium (VI) is an environmental and occupational carcinogen, and it is accepted that intracellular reduction is necessary for DNA damage and cytotoxicity. We have investigated the interaction of Cr(VI) with hepatocytes in vitro to determine the contribution of various hepatic enzymes to the reduction of Cr(VI). Cr(VI) caused a dose-dependent decrease in cell viability and intracellular reduced glutathione (GSH) levels between 100 and 500 μM within 3 h exposure of hepatocytes. Both DT-diaphorase and cytochrome P450 play only a minor role in detoxifying Cr(VI) and/or its metabolites. (GSH) appears to act as a non-enzymatic reductant, reducing Cr(VI) to a toxic form. The evidence for this is two-fold. Firstly, GSH was depleted during the metabolism of Cr(VI) and, secondly, pretreatment of the cells with diethylmaleate to deplete GSH levels, partially protected the cells from Cr(VI) toxicity. Glutathione reductase appears to play an important role in the enzymatic reduction of Cr(VI) as inhibition of this enzyme by carmustine (BCNU) markedly protected the cells from cytotoxicity.
    Original languageEnglish
    Pages (from-to)191-202
    Number of pages11
    JournalChemico-Biological Interactions
    Volume134
    Issue number2
    DOIs
    Publication statusPublished - 2001

    Keywords

    • chromium
    • toxicity
    • hepatocytes
    • glutathione reductase
    • reduced glutathione
    • bioengineering

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