, 2008). Thus, available data suggest that WC particles in association with Co particles, rather than WC or Co particles alone, should be considered a specific toxic combination in development of hard metal lung disease. The free radical formation has possible consequences of oxidative damage, as detected in the murine RAW 264.7 cell line using EPR spectroscopy. Particle size-dependent differences in ROS generation were observed for all study powders [tungsten (W), tungsten carbide

(WC, W2C), cobalt (Co) and admixture (WC, W2C and Co)] except Co alone, which did not generate radicals in the cellular model (Stefaniak et al., 2010). PD0325901 concentration When the dose of powders was normalized to surface area (expressed as m2/g), the formation of hydroxyl radicals was independent of particle size, suggesting that particle surface chemistry may be an important exposure

factor. Inhaled particles interact primarily with the lung surface made up by surfactants BTK inhibitor in vitro and antioxidants (Fenoglio et al., 2008). GSH acts as a ROS scavenger, thus constituting one of the first lines of defense against lung injury due to the over-production of ROS. Both ascorbic acid and GSH are able to scavenge superoxide and hydroxyl radicals. In addition, GSH and cysteine residues in proteins also have an important role in redox regulation. The concentration of GSH and Cys is significantly reduced in the presence of the Co/WC mixture, while the single components alone do not react or react to a much lesser extent with GSH and Cys. The extent of the reduction of the thiols concentration correlates to the amount of dust and, consequently, with the surface area exposed. The reactivity of Co/WC mixture with cysteine and thiols (GSH) is quite significant. Cysteine alone reacts with Co/WC more extensively than the cysteinyl fragment in the tripeptide GSH. The results are consistent with the oxidation occurring at the surface containing mainly cysteine S–H groups involved in the generation of sulphur-centered radicals. Such a reaction, will enhance the level of oxidative stress

caused by particles and cell-generated free radicals (Stefaniak et al., 2009). A detailed experiment on particle surface chemistry elucidated the importance of close contacts of metals with biologically active surface area Florfenicol in the formation of free radicals by particle mixtures. Interestingly, a reversed effect of cobalt on free radical generation has been reported (Shukla et al., 2009). Hypobaric hypoxia is accompanied by increased formation of free radicals and suppressed activities of antioxidant enzymes. Exposure of rats to hypobaric hypoxia revealed increased oxidation of lipids and proteins and decreased reduced oxidized glutathione (GSH/GSSG) ratio and increase in SOD, GPx, and GST levels. In addition, increase in heme oxygenase 1 (HO-1) and heat shock protein 70 (HSP70) was also recorded.