, 2010), which could be associated see more to a possible lower absorption of LASSBio 596 per os. As previously reported by Carvalho et al. (2010), using the intraperitoneal route,

treatment with LASSBio 596 per os avoided mechanical impairment, i.e., smaller ΔP1, ΔP2, ΔPtot, ΔE and Est in LASS than in TOX ( Fig. 2). Part of these findings can be explained by improved structural and functional changes of lung parenchyma as evidenced by morphometric and cellularity analysis ( Table 1 and Fig. 3). Indeed, a smaller area of alveolar edema, thinner septa and reduction of collapsed areas were found in LASS group than in TOX. In fact, LASSBio 596 per os rendered the results similar to those in CTRL. Accordingly, a significant improvement in the release of pro-inflammatory cytokines in lungs and liver was observed in LASS. Additionally, the histopathological analysis of the liver showed dilatation and congestion of sinusoids, hepatocellular disarray, loss of hepatic architecture, high level of binucleate or multinucleate hepatocytes, vacuolation and necrosis in TOX group. Indeed, the hepatotoxic effects of MCYST-LR contamination are widely described (Hooser et al., 1989, Fugiki, 1992, Camichael, 1994, Barreto et al., 1996, Azevedo et al., 2002 and Andrinolo et al., 2008). The pathological findings in LASS were less evident than in TOX group (Fig. 5).

This improvement could probably be explained by the significant less liver inflammation in LASS. In the present study we could not detect free MCYST-LR in the lungs, but it was present in the animals’ livers to a similar extent in both groups that

Selleck Dasatinib received MCYST-LR (Fig. 4). Staurosporine The liver is the target organ for microcystins, because of the ability of hepatocytes to uptake these toxins through bile acid transporters (organic anion transporting polypeptides) (Camichael, 1994 and Feurstein et al., 2009). A damaged liver can release inflammatory mediators causing a secondary lung inflammation (Nobre et al., 2001). Furthermore, inflammatory mediators (TNF-α e IL-1) can be produced by peritoneal macrophages after microcystin injection (Nakano et al., 1991). Thus, even if MCYST-LR did not reach the lungs in our model, probably the acute pulmonary inflammation was started off by cytokines produced by the damaged liver and peritoneal macrophages, which were carried by the blood stream. Another possibility is the direct action of MCYST-LR on lung cells. Thus, it is possible that a recirculation of toxin occurs, increasing MCYST toxicity (Ito et al., 2001 and Soares et al., 2007). In this context, alveolar macrophage stimulated by MCYST-LR can produce prostaglandins F2 and PGE2 as well as thromboxane B2 and arachidonic acid (Naseen et al., 1989). The toxin could also damage type II pneumocytes. Since our method did not allow the determination of bound MCYST-LR, it was not possible to confirm its presence in the lung under this form.