Glutathione reductase reduces chromium VI to cytotoxic metabolites in isolated rat hepatocytes

M. Gunaratnam, M.H. Grant

    Research output: Contribution to journalArticle

    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 microM 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)119-121
    Number of pages2
    JournalToxicology
    Volume168
    Issue number1
    DOIs
    Publication statusPublished - 2001

      Fingerprint

    Keywords

    • chromium
    • hepatocytes
    • cytotoxic metabolites
    • bioengineering

    Cite this