The high potential cytotoxicity means to be the reason for changi

The high potential cytotoxicity means to be the reason for changing the Idelalisib solubility dmso present limit, but few studies have

investigated it concerning aquatic vertebrates like fish. More specifically, studies focusing the effects of this compound to a target tissue such as the liver or the hepatocytes are scarce. The current study established a primary hepatocyte culture model from P. lineatus, which was utilized to investigate the cellular responses for realistic concentrations of purified cylindrospermopsin. The reduced MXR activity found in this work showed that the first-line defense mechanism, responsible for efflux xenobiotics, toxins, drugs and endobiotic metabolites ( Kurelec et al., 1992) was affected. Since cells normally respond to many forms of chemical stresses by increasing MXR activity in order to facilitate the efflux of toxic substances ( Gottesman and Pastan,

1993), the decreased MXR activity of hepatocytes suggests an possible cellular accumulation of substances up to toxic levels. As a consequence, cellular sensitization to other endobiotic or xenobiotic stressors could disturb the cellular homeostasis. Then, hepatocytes exposed to cylindrospermopsin were significantly more sensitive and may succumb more rapidly to ABT-199 eventual exposure to other xenobiotics or metabolites that are substrates to some of these ABC transporters. The liver depends on this system for xenobiotic efflux, and sensitization of hepatic cells increases the potential of liver failure. Also, the establishment of MXR system as a biomarker in cultured hepatocytes represents a valuable tool for investigation of complex mixtures effects. Higher production of reactive new oxygen/nitrogen species (RONS) due to cylindrospermopsin exposure may increase the potential damage to biomolecules such as lipids, proteins and even

DNA. Particularly, lipid peroxidation can alter membrane fluidity, permeability, transport and electric potential (Abuja and Albertini, 2001, Kühn and Borchert, 2002 and Prieto et al., 2007). As reported in the present study, the increased lipid peroxidation on hepatocytes exposed to the highest cylindrospermopsin concentration in comparison to the control group did not seem to be the cause of cell death. Indeed, cells may support a slight lipid peroxidation due to the robust protective mechanisms present in hepatocytes that may be activated to maintain cell viability. Apparently, other defense mechanisms besides the glutathione S-transferase (one enzyme responsible for lipid hydroperoxides degradation) and the glucose 6-phosphate dehydrogenase may be involved in this finding, since there were no differences in these enzymes activities in relation to the control group.

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