In all instances the significance level was set at 5% (p < 0.05). The treatment with LASSBio 596 per os significantly avoided the influx of PMN cells, airspaces collapse ( Table 1), as well as the rising of TNF-α, IL-6 and IL-1β levels in lung and liver tissues ( Fig. 1). Additionally, the elevated pulmonary mechanical parameters ( Fig. 2),

the presence of alveolar collapse, edema and alveolar septum thickness present in TOX Afatinib in vitro ( Fig. 3) were not observed in the LASS group. LASS and CTRL did not differ in any parameters studied. MCYST-LR was not detected in lung tissue, but free MCYST-LR was similarly detected in liver tissue in both LASS and TOX groups (Fig. 4), but not in CTRL. The disarray in liver architecture expressed by necrosis, inflammation, high degree of binucleated hepatocytes, cytoplasmatic vacuolization, dilated sinusoidal Epacadostat ic50 spaces and steatosis were less evident in the LASS than TOX group (Fig. 5). The main findings of the present study were: 1) the treatment with LASSBio 596 per os avoided lung and liver inflammation and pulmonary mechanical dysfunction found in TOX mice; 2) in addition a qualitative

improvement in liver structure was observed. It is known that MCYST-LR contamination leads to a direct liver insult followed by damage on several organs such as lung, kidney and intestine (Ito et al., 2001). However, acute lung injury related to MCYST-LR exposure is scantly assessed. Our group previously reported that respiratory system can be injured even by sub-lethal doses of MCYST-LR administered by pulmonary or extrapulmonary routes (Picanço et al., 2004 and Soares et al., 2007). This suggests that these toxins even Cediranib (AZD2171) when administered at low concentrations may be present in the circulation and directly trigger a network of inflammatory responses mediated by immune cells in many organs (Wang et al., 2008). MCYST-LR inhibits PP1 and 2A, yielding an unusual cellular protein phosphorylation, and, thus, possibly activates protein kinase C. The latter activates phospholipase

A2 and cyclooxygenase, triggering inflammation (Nobre et al., 2001, Nobre et al., 2003 and Kujibida et al., 2006). Moreover, the influx of PMN also yields to the release of pro-inflammatory cytokines and reactive oxygen species (ROS) that adds to the development of tissue injury (Moreno et al., 2005). When injected intraperitoneally LASSBio 596 seems effective in different models of acute lung injury, such as endotoxin model induced by lipopolysaccharide of E. coli, allergic sensitization to ovalbumin, ischemia and reperfusion, and also in acute lung injury induced by MCYST-LR ( Rocco et al., 2003, Campos et al., 2006, Morad et al., 2006 and Carvalho et al., 2010). In order to circumvent MCYST-LR undesirable effects, we have recently reported a possible treatment of pulmonary damage induced by acute exposure to MCYST-LR by the intraperitoneal administration of LASSBio 596 or dexamethasone ( Carvalho et al., 2010).