Protein carbonylation and DNA breaks are common biomolecules damages that can significantly interfere with cell functioning. However, cylindrospermopsin exposure did not alter these biomarkers in P. lineatus hepatocytes. Then, cell-type and interspecific cylindrospermopsin toxicity differences may occur, since exposure of mammal cells to the same concentrations of cylindrospermopsin led to concentration-dependent DNA damage ( Humpage et al., 2000 and Lankoff et al., 2007). GSK269962 The absence of protein and DNA damage are corroborated by unaltered levels of 2GSH/GSSG ratios. Consequently, there was not impairment of the synthesis and cycling of this

important non-enzymatic antioxidant and cofactor for glutathione-dependent enzymes involved

in xenobiotic biotransformation and peroxides buy Obeticholic Acid degradation (Arteel and Sies, 2001 and Van Bladeren, 2000). Then, although some authors reported that cylindrospermopsin decreased GSH concentrations in rat hepatocytes (Runnegar et al., 1995), the majority of studies on this issue indicate that impairment of GSH homeostasis is not the primary toxic mechanism of this toxin. Conversely, there is some data that indicate that biotransformation of cylindrospermopsin by cytochrome P450 may play a role in mammals (Norris et al., 2002). Finally, the increase of both lipid peroxidation in the hepatocytes exposed to highest toxin concentration (10 μg l−1) and RONS levels, and the decrease of cell viability in the two lowest concentrations (0.1 and 1 μg l−1) as well as the decreased of MXR activity in all tested concentrations represent important findings that must be considered in the cylindrospermopsin toxicity. Particularly, the decreased

MXR activity might have important consequences for cell survival due to accumulation of metabolites within cells. At the highest concentration, activation of other not investigated protective mechanisms by cylindrospermopsin may maintain the cell viability. However, we expect to observe different results if cells were exposed to unpurified cylindrospermopsin extracts or to the toxin associated with xenobiotics, since this mafosfamide toxin may make P. lineatus hepatocytes sensitive to other chemicals. In conclusion, the current study introduces the studies of cylindrospermopsin, an important toxin to Brazilian reservoirs, on primary cultured hepatocytes of Brazilian fish. Additionally, this work utilizes for the first time the activity of the MXR system as a ‘new biomarker’ in fish hepatocytes culture for investigation of cylindrospermopsin effects. The next step is to investigate if cylindrospermopsin can ease the effects of other xenobiotics in vitro. This is an important issue, since cyanobacteria proliferation is associated, at least in part, with the presence of other pollutants like urban dejects. The authors declare that there are no conflicts of interest.