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In vitro effect of arsenical compounds on glutathione related enzymes

Citation

Chouchane, S and Snow, ET, In vitro effect of arsenical compounds on glutathione related enzymes, Chemical Research in Toxicology, 14, (5) pp. 517-522 . ISSN 0893-228X (2001) [Refereed Article]

DOI: doi:10.1021/tx000123x

Abstract

The mechanism of arsenic toxicity is believed to be due to the ability of arsenite (AsIII) to bind protein thiols. Glutathione (GSH) is the most abundant cellular thiol, and both GSH and GSH-related enzymes are important antioxidants that play an important role in the detoxification of arsenic and other carcinogens. The effect of arsenic on the activity of a variety of enzymes that use GSH has been determined using purified preparations of glutathione reductase (GR) from yeast and bovine glutathione peroxidase (GPx) and equine glutathione S-transferase (GST). The effect on enzyme activity of increasing concentrations (from 1 μM to 100 mM) of commercial sodium arsenite (AsIII) and sodium arsenate (AsV) and a prepared arsenic(III)-glutathione complex [AsIII(GS)3] and methylarsenous diiodide (CH3AsIII) has been examined. GR, GPx, and GST are not sensitive to AsV (IC50 > 50 mM), and none of the enzymes are inhibited or activated by physiologically relevant concentrations of AsIII, AsIII(GS)3, or CH3AsIII, although CH3AsIII is the most potent inhibitor (0.3 mM < IC50 < 1.5 mM). GPx is the most sensitive to arsenic treatment and GST the least. Our results do not implicate a direct interaction of As with the glutathione-related enzymes, GR, GPx, and GST, in the mechanism of arsenic toxicity. CH3AsIII is the most effective inhibitor, but it is unclear whether this product of arsenic metabolism is produced at a sufficiently high concentration in critical target tissues to play a major role in either arsenic toxicity or carcinogenesis.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Pharmacology and Pharmaceutical Sciences
Research Field:Toxicology (incl. Clinical Toxicology)
Objective Division:Health
Objective Group:Public Health (excl. Specific Population Health)
Objective Field:Environmental Health
Author:Snow, ET (Associate Professor Elizabeth Snow)
ID Code:43710
Year Published:2001
Web of Science® Times Cited:70
Deposited By:Health Sciences A
Deposited On:2007-10-30
Last Modified:2011-09-29
Downloads:0

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