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Inhibition of glutathione reductase by chromium (VI)

Bibi, S. and Angeli, F. and Grant, M.H. (2004) Inhibition of glutathione reductase by chromium (VI). In: Proceedings of the British Pharmacological Society Conference 2004. British Pharmacological Society.

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Chromium (VI) compounds have serious toxic and carcinogenic effects in humans. To exert toxicity and carcinogenicity Cr (VI) must be reduced inside cells, and it can be reduced both enzymatically and non-enyzmatically. Glutathione reductase (GR) has been implicated in the intracellular reduction of Cr (VI). This enzyme normally re-cycles reduced glutathione (GSH) from oxidized glutathione (GSSG), and is essential for protecting cells against intermediates which deplete GSH, and against oxidative stress. During its reduction inside cells Cr (VI) disrupts redox balance, and generates reactive oxygen species. These oxidize GSH and deplete reduced thiols, leading to toxicity and carcinogenesis. Susceptibility to Cr (VI) will depend on the ability of cells to protect themselves by recycling GSH via GR. The effect of exposure to Cr (VI) in vitro on the activity of GR in cells derived from liver (Hep G2 cells), colon (HT 115 cells), larynx (Hep 2 cells) and macrophages (J774.1 cells) was investigated.