Sublethal doses can cause lesions that include hepatocellular hyp

Sublethal doses can cause lesions that include hepatocellular hypertrophy, intracytoplasmic eosinophilic inclusions and apoptosis (Guzman and Solter, 2002). However, it is well known that MCYSTs can also affect other organs and tissues (Humpage, 2008; Wang et al., 2008). Moreover, several studies have confirmed that prolonged exposure to low doses can promote tumors

in tissues such as the colon, skin and liver (Falconer and Humpage, 1996; Ito et al., 1997). These toxins can enter the cell through a group of organic anion transporting polypeptides (OATP). Members of the multispecific OATP family can be detected in nearly all tissues in humans, rodents E7080 manufacturer and other animals, although they are less expressed in most non-liver Epacadostat concentration cells (Fischer et al., 2005). They play an important role in the absorption, distribution and excretion of numerous xenobiotic molecules (Hagenbuch and Meier, 2003). Recently, Fischer et al. (2010) described different affinities between MCYST congeners and specific

OATPs. Kidney expresses OATPs and is one of the organs affected after exposure to MCYSTs (Wang et al., 2008). It also plays a role in excretion of the toxin (Ito et al., 2002), but the mechanisms of nephrotoxicity are not completely known. Some in vitro studies on kidney epithelial cells showed that higher doses cause similar effects to those observed in hepatocytes, mostly related to cytoskeleton disarrangement (Khan et al., 1995 and Khan et al., 1996). Studies on Vero cells showed that a mild MCYST concentration leads to early effects (vacuolization) on endoplasmic reticulum, probably related to an autophagy process as part of a cell response to the aggression (Alverca et al., 2009). Moreover, those cells under lower concentrations showed increased proliferation, which suggests the potential tumor promotion effect of MCYST on renal cells (Dias et al., 2010). In renal tissue, maldevelopment of glomeruli and renal medulla was observed in fetuses from female rats injected find more intraperitoneally (i.p.) daily

with 62 μg/kg body weight (bw) for 10 days (Zhang et al., 2002). In addition, Nobre et al., 1999, Nobre et al., 2001 and Nobre et al., 2003 demonstrated the involvement of an inflammatory process on MCYST-derived nephrotoxicity in perfused rat kidneys. An increasing number of therapeutic agents has been recognized as nephrotoxic and a wide variety of chemical pollutants, along with environmental chemicals (mycotoxins and botanicals, for example), was already described causing renal toxicity (Goldstein and Schnellmann, 1996). However, although kidney seems to be an important affected organ, there is not much knowledge on the sublethal injurious effects of MCYST on renal physiology. Hence, this work assesses aspects of renal metabolism, oxidative stress and histopathology of Wistar rats exposed to a sublethal dose of purified MCYST-LR. Deionized water through Milli-Q resins (Millipore Corp., Marlborough, MA) was used to prepare all solutions.