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

Gunaratnam, M. and Grant, M.H. (2001) Glutathione reductase reduces chromium VI to cytotoxic metabolites in isolated rat hepatocytes. Toxicology, 168 (1). pp. 119-121. ISSN 0300-483X

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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.

Item type: Article
ID code: 6774
Keywords: chromium, hepatocytes, cytotoxic metabolites, bioengineering, Bioengineering, Human anatomy, Toxicology
Subjects: Technology > Engineering (General). Civil engineering (General) > Bioengineering
Science > Human anatomy
Department: Faculty of Engineering > Bioengineering
Related URLs:
Depositing user: Strathprints Administrator
Date Deposited: 28 Aug 2008
Last modified: 04 Sep 2014 14:22
URI: http://strathprints.strath.ac.uk/id/eprint/6774

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