, 2009 and Olivant Fisher et al., 2012). In contrast, iNOS is expressed in white blood cells in response to pathogens, resulting in overproduction of nitric oxide and a

pro-oxidant state Quizartinib cell line (Gutteridge and Mitchell, 1999). In the present study, no significant differences were observed in iNOS expression between CLP–SAL and CLP–DEXA groups, which may be attributed to the moment of dexamethasone administration, early in the course of inflammation (Thakur and Baydoun, 2012). Even though it has been described that dexamethasone may regulate iNOS expression exclusively through NF-κB (Jantz and Sahn, 1999), a recent study reported that dexamethasone enhanced iNOS gene expression but repressed iNOS protein with no noticeable effects on NF-κB (Thakur and Baydoun, 2012). OA increased expression of SOD and prevented an increase in iNOS, with no significant changes in Nrf2, GPx, and CAT. In this context, recent studies have shown that increases in SOD (Siedlinski et al., 2009 and Olivant Fisher et al., 2012) and decreases in iNOS (Soejima et al., 2000 and Pittet et al., 2001) correlate

with a reduction in lung damage. Additionally, OA is a free radical scavenger, acting through direct chemical reactions (Wang et al., 2010) and iNOS inhibition, preventing the overproduction of nitric oxide and depletion of intracellular glutathione and cytotoxicity (Abdel-Zaher et al., 2007). The unchanged pattern of Nrf2 expression after OA administration (Fig. 3) contradicts the findings of previous in vitro ( Reisman et al., 2009 and Wang et al., 2010) and in vivo ( Liu et al., 2008)

studies showing an BKM120 mw increase in the expression of Nrf2. These divergent results may be attributed to the dose and frequency of OA administration. In agreement with the present study, GPx levels were not found to change in a CLP-induced sepsis model ( Andrades et al., 2011) or in septic patients ( Lang et al., 2002), which may be explained by a delay in GPx upregulation ( Comhair et al., 2001). Even though GPx and CAT are the most important H2O2 scavenging enzymes, other enzymes, such as glutaredoxins, peroxiredoxins, and thioredoxins, may play a role in H2O2 degradation in the lung ( Kinnula and Crapo, 2003). In the model of CLP-induced sepsis used HSP90 herein, IL-6 and KC did not change after OA administration, but reductions were observed in other ARDS models (Lee et al., 2010 and Santos et al., 2011). Accordingly, in our previous study (Santos et al., 2011), oleanolic acid reduced IL-6 in experimental ARDS induced by paraquat, which results in a pro-oxidative model (Dinis-Oliveira et al., 2008). These differences can be explained by the timing of analysis and choice of model, since the pathophysiology of ARDS may differ according to the primary insult. Dexamethasone decreased IL-6 and KC, but did not modify oxidative stress mediators.