, 1983; Griffiths and Saker, 2003; Berry et al., 2009). Since that time a great deal of attention has been dedicated to cylindrospermopsin, although there is no data in the literature reporting the dose-dependence of human beings to that toxin. Poisoning resulted from recreation ( Chorus et al., 2000; Rao

et al., 2002) and possible accumulation in the food-web ( Saker and Eaglesham, 1999); transmission from mice females to their fetuses ( Paerl et al., 2001; Codd et al., 2005; Falconer and Humpage, 2006; Rogers et al., 2007) has also been reported. Owing to its high solubility in water and low rate of bio- Ceritinib solubility dmso and photodegradation, significant amounts of cylindrospermopsin can be expected to occur in the water column (Wormer et al., 2008, 2010). The toxin concentrations in the European environment were found to amount up to 12.1 μg/L in Germany (Rücker et al., 2007), up to 9.4 μg/L in Spain (Quesada GPCR Compound Library manufacturer et al., 2006), and up to 18.4 μg/L in Italy (Bogialli et al., 2006). US EPA classified cylindrospermopsin as

a compound with high priority for hazard characterization (U.S. Environmental Protection Agency, 2001). Despite considerable research, much remains to be disclosed with respect to the toxicity of cylindrospermopsin. It is known that the toxin irreversibly inhibits protein synthesis. However, the mechanisms involved in its toxicity and metabolism are not well understood. Terao et al. (1994) reported ribosome detachment from the rough endoplasmic reticulum, and the linkage of an active metabolite

of cylindrospermopsin to DNA or RNA, with consequent blockage of translation, was also suggested (Shaw et al., 2000). Cylindrospermopsin can also induce DNA fragmentation, chromosome losses, and possibly carcinogenicity (Humpage et al., 2000, 2005; Falconer and Humpage, 2001; Shen et al., 2002). Cylindrospermopsin toxicity seems to present two toxic responses (Falconer, 2008): The rapid toxicity appears to be mediated by CYP450 activation, which generates more toxic metabolites, while the longer-term toxicity is due to protein synthesis inhibition (Humpage et al., Paclitaxel nmr 2005). Although lethal doses of cylindrospermopsin can damage the liver, kidney, lung, heart, stomach and the vascular system (Hawkins et al., 1985), there are no reports in the literature investigating in vivo pulmonary damage produced by sub-lethal doses of cylindrospermopsin. Moreover, the understanding of the effects of these doses of the toxin is relevant because human beings are often exposed to low doses of cyanotoxins. Hence, in the present study we aimed at verifying whether a single sub-lethal dose of cylindrospermopsin can induce lung injury, and establish its putative dependence on the time elapsed since exposure. BALB/c male mice (6–7 week of age) were purchased from CEMIB (Multidisciplinary Center for Biological Investigation, University of Campinas, Campinas, Brazil).