While L-selectin expression was not altered by HQ intoxication (Fig. 6A), constitutive levels of β2 and β3 integrins and PECAM-1 were

significantly GSI-IX enhanced in neutrophil membranes (Fig. 6B, C and D, respectively). In addition, levels of L-selectin, β2 and β3 integrins and PECAM-1 were enhanced after in vitro fMLP stimulation in neutrophils obtained from vehicle-exposed animals. In contrast, these enhancements were not observed in neutrophils collected from HQ-exposed mice ( Fig. 6B, C and D, respectively). Epidemiological studies have associated the pivotal role of environmental pollutants with the genesis of a variety of human diseases, and special attention has been paid to exposure to low concentrations of pollutants, even lower than those allowed by international regulatory agencies (NIOSH, OSHA). In this context, in vivo Gefitinib studies with experimental animals have contributed to extending our knowledge of mechanism of actions of toxicants. Based on the data presented here, we showed that low levels of in vivo exposure to HQ impairs LPS-induced host defense by interfering with blood neutrophil trafficking, notably modifying the expression of adhesion molecules. The American Conference of Industrial Hygienists (ACGIH) and the National

Institute of Occupational Safety & Health (NIOSH) defines 2 mg/m3 (0.44 ppm) TWA for HQ (WHO, 1994 and NIOSH, 1994) as non hazardous exposure. Although we did not correlate human and animal exposures, it is conceivable that in this oxyclozanide study mice were subjected to low levels of HQ, as defined by the air concentrations in the exposure chamber (0.044 ppm). Our subsequent studies reinforced such point of view, by observations that relevant biochemical and biological end-points described in the literature for in vivo exposure to BZ or HQ, as the number of circulating leukocytes and their DNA integrity ( Bi et al., 2010, McGregor, 2007, Macedo et al., 2006 and Medeiros et al., 1997), were not affected by the experimental intoxication procedure

employed here. In vitro exposure to HQ causes oxidative damage in different cell types, including leukocytes, and DNA lesions are employed as toxic end points ( Ji et al., 2009, Varkonyi et al., 2006, Gaskell et al., 2004, Gaskell et al., 2005a and Gaskell et al., 2005b). The mechanism is based on HQ biotransformation into semiquinones via redox cycling which induces ROS production, including superoxide anion radical (O2 −), hydrogen peroxide (H2O2), nitric oxide (NO ) and hydroxyl radical (OH ) ( Winn, 2003). Here, we demonstrated that even low concentrations of in vivo exposure to aerosolized HQ evoked the activation of oxidative pathways, as measured by plasma MDA levels and ROS production by circulating cells. Nevertheless, oxidative stress was not accompanied by DNA fragmentation.