title: Synergistic neurotoxicity of oxygen-glucose deprivation and tetrabromobisphenol A in vitro: role of oxidative stress.
abstract: BACKGROUND
  Tetrabromobisphenol A (TBBPA) is a toxic brominated flame retardant. Previous studies have demonstrated that exposure of primary cultures of rat cerebellar granule cells (CGC) to ≥ 10 μM TBBPA induces toxicity and excitotoxicity, and the underlying mechanism may involve calcium imbalance and oxidative stress. Here we examined whether the application of TBBPA at subtoxic concentrations may exacerbate acute damage of CGC challenged with oxygen-glucose deprivation (OGD), and evaluated with fluorescent indicators the involvement of calcium imbalance, mitochondrial depolarization and oxidative stress.
  
  
  METHODS
  Survival of CGC was assessed 24 h after OGD/TBBPA using fluorescent dyes. An OGD challenge lasting for 45, 60 or 75 min induced a duration-dependent injury to the neurons.
  
  
  RESULTS
  Application of 2.5, 5 or 7.5 μM TBBPA for 45 min to normoxic and glucose-containing incubation medium did not reduce the viability of cultured CGC, but this compound exacerbated the toxic effects of OGD in a concentration-dependent way. Moreover, TBBPA had a slight effect on calcium homeostasis and mitochondrial membrane potential, but significantly activated the production of reactive oxygen species in CGC. The application of H(2)O(2) at 5, 10 and 25 μM mimicked the effects of TBBPA on OGD toxicity, while 0.1 mM ascorbic acid or 1 mM glutathione ameliorated this toxicity.
  
  
  CONCLUSIONS
  These results suggest the involvement of oxidative stress in the synergistic neurotoxic effects of TBBPA and OGD.
authors.affiliation: Mossakowski Medical Research Centre, Polish Academy of Sciences, Pawińskiego 5, PL 02-106 Warszawa, Poland. elkaz@cmdik.pan.pl
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Ziemińska
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Stafiej
authors.forename: Beata
authors.initials: B
authors.lastname: Toczyłowska
authors.forename: Jerzy W
authors.initials: JW
authors.lastname: Lazarewicz
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D015687:Cell Hypoxia; D002470:Cell Survival; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D018384:Oxidative Stress; D011075:Polybrominated Biphenyls / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D011075:Polybrominated Biphenyls; D017382:Reactive Oxygen Species; C020806:tetrabromobisphenol A; D005947:Glucose; D002118:Calcium