Intensive production of synthetic polymer-based materials such as polyvinyl chloride, phenolic and melamine plastics, polystyrene, polyethylene or fibre-forming polymers involves the use of compounds having an inhibitory effect on the ignition of the materials, which aims enhancing their safety of use. So far approx. 70 bromine compounds are used as flame-retarding substances. Several studies have suggested that some brominated flame retardants (BFRs) could potentially pose a risk to human health. Tetrabromobisphenol A (TBBPA) is the most widely used compound among BFRs. Products with both additive and chemically bonded forms of TBBPA have been shown to release it into the environment. Although studies indicate high metabolism of TBBPA in rats and humans owing to rapid conjugation with glucuronic acid and elimination in the bile, TBBPA has been detected in cow and human milk, human serum, human adipose tissue and umbilical cord serum. Due to its structural homology with bisphenol A, TBBPA is a candidate to be one of some endocrine disruptors. TBBPA was also shown to accumulate in different brain regions and to induce the behavioral alterations (Nakajima et al. 2009). Some in vivo studies suggest that exposure to TBBPA during the perinatal period may affect locomotor activity and/ or memory and learning. However, only few studies have been undertaken to investigate the mechanism of TBBPA neurotoxic effects. Recently, it was demonstrated that TBBPA could act as the PPAR-γ ligand in NIH3T3-L1 cells (Riu et al. 2011). The aim of the present study was to investigate the effect of TBBPA on viability of cultured hippocampal mouse neurons. Additionally, the role of PPAR-γ in TBBPA-induced cytotoxicity of hippocampus neurons was studied. The cultures of hippocampal neurons were prepared from Swiss mouse embryos on 17/18 days of gestation. The cells were cultured in phenol red-free Neurobasal medium supplemented with glutamine and B27 onto poly-ornithinecoated plates. For experiment cells were exposed to TBBPA in a following concentrations: 1, 10, 50, 100 nM, and 1, 10, 50 and 100 μM. To study the involvement of PPAR-γ in mechanism of TBBPA action the specific agonist GW1929 and antagonist GW9662 were used. Cell cultures were exposed to experimental dose of TBBPA for 6 hours and after this time media were collected for measurement of LDH activity. Our study for the first time demonstrated that TBBPA in a wide range of concentrations stimulated, in a dose-dependent manner, the LDH activity in the cultured mouse hippocampal cells. Moreover, the cytotoxic effect of TBBPA was diminished by the addition of both PPAR-γ agonist and antagonist. The presented results suggest that neurotoxic effects of TBBPA are mediated by PPAR gamma. This study implicates this receptor as a novel toxicity target for TBBPA in neuronal cells. This work was supported by the University of Agriculture in Krakow, Poland, DS No 3242/12 .
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