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. 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.
Fenoglio
Ivana
I
Dipartimento di Chimica Inorganica, Chimica Fisica e Chimica dei Materiali, Interdepartmental Center G Scansetti for Studies on Asbestos and Other Toxic Particulates, Universita degli Studi di Torino, Torino, Italy.
Corazzari
Ingrid
I
Francia
Carlotta
C
Bodoardo
Silvia
S
Fubini
Bice
B
D003035:Cobalt / Q000633:toxicity*; D004563:Electrochemistry; D004578:Electron Spin Resonance Spectroscopy; D005978:Glutathione / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D014131:Trace Elements; D017973:Tungsten Compounds / Q000633:toxicity*; D019820:Xanthine / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism
D017382:Reactive Oxygen Species; D014131:Trace Elements; D017973:Tungsten Compounds; D013481:Superoxides; C002802:tungsten carbide; D019820:Xanthine; D003035:Cobalt; D014969:Xanthine Oxidase; D005978:Glutathione