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Original

The oxidation of glutathione by cobalt/tungsten carbide contributes to hard metal-induced oxidative stress

, , , &
Pages 437-745 | Received 06 May 2008, Published online: 07 Jul 2009
 

Abstract

The occupational exposure to cobalt/tungsten carbide (Co/WC) dusts causes asthma and interstitial fibrosis. The International Agency for Research on Cancer (IARC) recently classified the mixture Co/WC as probably carcinogenic to humans (group 2A). The mechanism of action of Co/WC involves particle driven generation of Reactive Oxygen Species (ROS) with consequent oxidative damage. The present study evaluates the reactivity of Co/WC dust toward glutathione (GSH) and cysteine (Cys). Co/WC oxidized thiols through a mechanism involving the generation of sulphur-centred radicals. The results are consistent with the oxidation taking place at surface active sites, a part of which is accessible only to Cys S-H groups, but not to GSH ones. Such a reaction, with consequent irreversible depletion of antioxidant defenses of cells, will potentiate the oxidative stress caused by particle and cell generated ROS.

Abbreviations
ROS=

Reactive Oxygen Species

DEPMPO=

5-(diethoxyphosphoryl)-5-methyl-1-pyrroline-N-oxide

PB=

phosphate buffer

Abbreviations
ROS=

Reactive Oxygen Species

DEPMPO=

5-(diethoxyphosphoryl)-5-methyl-1-pyrroline-N-oxide

PB=

phosphate buffer

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