In this study the attempt to assess nephrotoxicity of TBBF-A after repeated exposure was made, on the basis of selected biochemical parameters.
PL
Celem pracy było określenie wpływu tetrabromobisfenolu-A (TBBF-A) podawanego wielokrotnie szczurom na wybrane wskaźniki działania nefrotoksycznego. Obniżenie diurezy dobowej obserwowane w początkowym okresie doświadczenia wywołały dawki 50 i 250 mg/kg, natomiast wzrost tego parametru zaobserwowano po 14-krotnym podaniu szczurom dawki najniższej (10 mg/kg). Przeprowadzone oznaczenia stężenia białka w moczu wykazały nieznaczne jego podwyższenie wywołane podaniem dwóch wyższych dawek. Nasilenie wydalania nabłonków nerkowych z moczem (liczba Addisa) wywołało 21-krotne podanie TBBF-A w dawce 250 mg/kg. W doświadczeniu zanotowano 20% wzrost stężenia GSH w nerkach spowodowany podaniem najniższej dawki badanego związku. Wielokrotne podawanie TBBF-A szczurom spowodowało nieznaczne uszkodzenie nerek, które przejawiało się wzrostem stężenia białka całkowitego w moczu i nasileniem wydalania nabłonków nerkowych z moczem; zmiany tych parametrów świadczą o uszkodzeniu zarówno kłębków, jak i kanalików nerkowych.
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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The aim of this study was to identify, among selected environmental toxins, the substance with the highest in vitro toxicity to neurons combined with the most marked induction of calcium imbalance, oxidative stress and mitochondrial dysfunction. Exposure of primary cultures of rat cerebellar granule cells for 30 min to polychlorinated biphenyls (PCBs) or brominated flame retardants (BFRs) at concentrations of 10-50 µM identified tetrabromobisphenol A as the compound with the highest toxicity. At a concentration of 25 µM, apart from the moderate activation of ⁴⁵Ca uptake, this BFR induced the most pronounced increase in intracellular Ca²⁺ concentration, depolarization of mitochondria, and activation of ROS production.
The aim of this study was to complete research on the porphyrogenic effect of hexabrombenzene (HBB) and tetrabromobisphenol-A (TBBP-A). Experiments were performed on female Wistar rats. The examined compounds were administered in sunflower oil intragastrically in 3 doses. The determination of porphyrins in tissues was carried out by means of high-performance liquid chromatography. Repeated HBB administration caused a 3-8 times increase of total concentration of high carboxylated porphyrins (octa- and heptacarboxyporphyrins). The concentrations of these porphyrins were significantly lower in the liver of rats exposed to tbbp-a. However, in the kidneys significant alterations in porphyrins concentrations concerned only HBB.
W pracy sprawdzono wpływ jednorazowego podania myszom tetrabromobisfenolu-A na stężenie GSH i MDA w wątrobie oraz aktywność AlAT i ɣ-GT w surowicy. Zbadano także zanik [ 14C] tetrabromobisfenolu-A i jego kowalencyjnie związanych adduktów w wątrobie myszy. Zaobserwowano statystycznie znamienne obniżenie stężenia GSH i wzrost MDA oraz wzrost aktywności ɣ-GT.
EN
The aim of the study was to determine the effect of single administration of tetrabromobisphenol-A (TBBP-A) on the selected indicators of hepatotoxicity in mice. The decrease of GSH concentration (the most pronouced after the highest dose) and MDA level increase were noted 12, 24 and 120 hours following the administration. ɣ-GT activity in mice serum following all applied doses was higher than that for control groups. The activity of AlAT underwent only minor changes as compared with control. The single administration of TBBP-A to mice resulted in weak hepatotoxicity; it was manifested mainly by 5-fold increase of ɣ-GT activity and 3-fold decrease of MDA concentration. Both ɣ-GT and MDA were found to be more sensitive indicators of TBBP-A toxicity than other parameters tested in the study.
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