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The oxidation of glutathione by cobalt/tungsten carbide contributes to hard metal-induced oxidative stress
Authors:Ivana Fenoglio  Ingrid Corazzari  Carlotta Francia  Silvia Bodoardo  Bice Fubini
Affiliation:1. Dipartimento di Chimica Inorganica, Chimica Fisica e Chimica dei Materiali and Interdepartmental Center ‘G. Scansetti’ for Studies on Asbestos and Other Toxic Particulates, Università degli Studi di Torino, via Pietro Giuria 7, 10125, Torino, Italy;2. Dipartimento di Scienza dei Materiali e Ingegneria Chimica, Politecnico di Torino, Corso Duca degli Abruzzi, 24, 10129, Torino, Italy
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.
Keywords:Glutathione  hard metals  free radicals  particle toxicity  Co/WC
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