Tris-(2,3-dibromopropyl) isocyanurate induces depression-like behaviors and neurotoxicity by oxidative damage and cell apoptosis <i>in vitro</i> and <i>in vivo </i>

Abstract

-Tris-(2,3-dibromopropyl) isocyanurate (TDBP-TAZTO), an emerging brominated flame retardant, possesses the characteristics of candidate persistent organic pollutants and has displayed toxicity to fish and rodents. TDBP-TAZTO can pass through the blood-brain barrier and accumulate in the brain. TDBP-TAZTO might also induce neuronal cell toxicity. However, the neurotoxicity and mechanisms of TDBP-TAZTO have not yet been studied. We hypothesize that TDBP-TAZTO could induce neurotoxicity in mouse hippocampal neurons and SH-SY5Y cells. The mice were exposed to TDBP-TAZ-TO of 5 and 50 mg/kg by gavage, daily for 30 days. TDBP-TAZTO resulted in depression-like behaviors, which may be related with TDBP-TAZTO-induced upregulation of oxidative stress markers and overexpression of pro-apoptotic proteins in hippocampus. Furthermore, TDBP-TAZTO treatment for 48 hr (12.5, 25 and 50 μM) damaged SH-SY5Y cells, and led to cell apoptosis and oxidative stress in concentrationdependent manner. Our findings suggested that cell apoptosis and oxidative stress are important mechanisms in neurotoxicity induced by TDBP-TAZTO.

Tris (2,3-Dibromopropyl) Isocyanurate (TDBP-TAZTO or TBC) Shows Different Toxicity Depending on the Degree of Differentiation of the Human Neuroblastoma (SH-SY5Y) Cell Line

“…The reports show that the production of household materials such as electronics or plastic causes the release of many toxic substances, such as BFRs (Li et al 2015). BFRs are able to cross the blood-brain barrier and accumulate in animals' brains affecting their cells (Dong et al 2015). Therefore, due to the emerging problem of environmental pollution, in this study, we have determined the impact of TDBP-TAZTO on the neuron differentiation process in vitro and its engagement in the toxic mechanism in such cells.…”

“…Interestingly, our results showed that TDBP-TAZTO at the concentrations of 1, 10, 50, and 100 µM decreased resazurin reduction in the undifferentiated cells and in cells differentiated for 7 and 14 days. There are only a few reports in the literature describing the in vivo and in vitro toxicity of TDBP-TAZTO (Ruan et al 2009;Li et al 2011;Dong et al 2015), but our study is the first to use the LDH release parameter to assess the toxicity of the compound. To date, an in vivo experiment has demonstrated that TDBP-TAZTO at a concentration of 1 µg/mL was toxic to developing zebrafish (Danio rerio) embryos after 72 h of exposure (Li et al 2011).…”

“…In vitro studies demonstrated that TDBP-TAZTO was toxic at concentrations of 5-10 µM in primary cultures of the neurons of developing cerebellar granule cells but not in mature cerebellar granule neurons in rats (Qu et al 2011). Moreover, TDBP-TAZTO at concentrations of 12.5, 25, and 50 µM damaged human neuroblastoma cells SH-SY5Y cells and led to apoptosis and severe oxidative stress (Dong et al 2015).…”

“…The first described the use of TDBP-TAZTO dates back to 1959 when it was used in styrene as a flame retardant (Dong et al 2015). The annual TDBP-TAZTO production in China in the 1990s was estimated at over 500 metric tons (Li et al 2011).…”

“…Unfortunately, the molecular mechanism of the TDBP-TAZTO action has not been elucidated. Some research groups see a key role of oxidative stress in the TDBP-TAZTO mechanism of action (Dong et al 2015). However, further research is needed to understand this mechanism.…”