Tetrabromobisphenol A-induced oxidative stress in primary cultures of rat cerebellar granule cells:triggering role of CA2plus imbalance

• Autorzy: Zieminska E. , Lenart J. , Lazarewicz J.W.
• Języki publikacji: EN

Abstrakty

EN

BACKGROUND AND AIMS: Brominated flame retardant tetrabromobisphenol A (TBBPA) contaminates the environment and displays cytotoxic potential. The mechanism of its cytotoxicity in neurons encompasses interference with NMDA and ryanodine receptors (NMDARs and RyRs) resulting in increase in intracellular Ca2+ concentration (Ca2+i), and induction of oxidative stress, which may be primary, or secondary to rises in Ca2+i. The aim of this study was to assess the role of excitotoxicity and Ca2+ imbalance in TBBPA-evoked oxidative stress and cytotoxicity in neurons. METHODS: Using the primary cultures of rat cerebellar granule cells (CGC) we evaluated oxidative stress induced by an acute challenge with 10 or 25 µM TBBPA by measuring reactive oxygen species (ROS) production, intracellular glutathione (GSH) level, SOD-1 and SOD-2 level, catalase activity, and the level of Zn2+ in CGC. Zn2+ and Ca2+i were measured fluoromertically, moreover TBBPA toxicity 24 h after the exposure was evaluated using propidium iodide staining. The pharmacological tools included NMDARs antagonist MK-801, ryanodine with bastadin 12 inhibiting RyRs, and various free radical scavengers. RESULTS: TBBPA induced concentration-dependent decrease in CGC viability, increase in Ca2+i and Zn2+ level, in ROS production, decrease in GSH level, catalase activity and SOD-2 level. Co-application of NMDARs and RyRs inhibitors which completely prevented increase in Ca2+i, resulted in a significant, but not complete cytoprotection, and only partially reduced the oxidative stress in the CGC. Also administration of ROS scavengers provided only partial cytoprotection and reduction of oxidative stress. CONCLUSIONS: We conclude that the production of free radicals resulting secondarily from TBBPA-evoked excitotoxicity and increases in Ca2+ level together with oxidative stress possibly induced primarily by TBBPA, both participate in TBBPA cytotoxicity in cultured neurons. Supported by the NCN grant 2012/05/B/NZ7/03225.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2015
• Tom: 75
• Numer: Supl.
• Opis fizyczny: p.S37

Twórcy

autor

Zieminska E.

• Department of Neurochemistry, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Lenart J.

• Department of Neurochemistry, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Lazarewicz J.W.

• Department of Neurochemistry, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland