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

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.Theresults areconsistent withtheoxidationtaking placeatsurfaceactivesites,apartofwhichisaccessible onlyto 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.